73466-12-3

Basic information

• Product Name: (-)-LEUKOTRIENE A4 METHYL ESTER
• Synonyms: (-)-LEUKOTRIENE A4 METHYL ESTER;LEUKOTRIENE A4 METHYL ESTER;5S-TRANS-5,6-OXIDO-7E,9E,11Z,14Z-EICOSATETRAENOIC ACID, METHYL ESTER;(-)-leukotriene A4;LEUKOTRIENE A4-METHYLESTER SOLUTION (100UG/ML HEXANE/1% TRIETHYLAMINE);LTA4 (Leukotriene A4 methyl ester);PWXYNAKNLZUYAL-WAQVJNLQSA-N
• CAS NO: 73466-12-3
• Molecular Formula: C₂₁H₃₂O₃
• Molecular Weight: 332.48
• Mol File: 73466-12-3.mol
• Article Data: 20

Chemical Properties

• Appearance: /triethylamine:hexane solution
• Storage Temp.: −20°C
• CAS DataBase Reference: (-)-LEUKOTRIENE A4 METHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-LEUKOTRIENE A4 METHYL ESTER(73466-12-3)
• EPA Substance Registry System: (-)-LEUKOTRIENE A4 METHYL ESTER(73466-12-3)

Safety Data

• Hazard Codes: F,Xn,N
• Statements: 11-36/37/38-48/20-51/53-62-65-67
• Safety Statements: 9-16-29-33-36/37-61-62
• RIDADR: UN 1208 3/PG 2
• WGK Germany: 2
• Hazardous Substances Data: 73466-12-3(Hazardous Substances Data)

Usage

Description

(-)-Leukotriene A4 Methyl Ester (LTA4) is a stable derivative of the naturally occurring unstable intermediate Leukotriene A4, which plays a crucial role in the biosynthesis of Leukotriene B4 (LTB4) and Leukotriene C4 (LTC4). LTA4 is synthesized in various immune cells, such as mast cells, eosinophils, and neutrophils, from arachidonic acid by 5-lipoxygenase (5-LO), an enzyme with both lipoxygenase and LTA4 synthase activities. The methyl ester form of LTA4 is stable and can be easily hydrolyzed to the free acid when required.

Uses

Used in Pharmaceutical Industry:
(-)-Leukotriene A4 Methyl Ester is used as a key intermediate compound for the synthesis of other biologically active leukotrienes, such as LTB4 and LTC4. These leukotrienes are involved in various physiological processes, including inflammation, immune response, and blood clotting. The study and development of LTA4 and its derivatives can lead to the creation of new therapeutic agents for treating conditions related to these processes.
Used in Research and Development:
In the field of biomedical research, (-)-Leukotriene A4 Methyl Ester serves as an important tool for understanding the role of leukotrienes in cellular signaling and their involvement in various diseases. Researchers can use LTA4 as a stable source to study the enzymatic reactions and pathways involved in leukotriene biosynthesis, as well as to investigate the potential therapeutic applications of leukotrienes and their analogs.
Used in Drug Delivery Systems:
Similar to gallotannin, (-)-Leukotriene A4 Methyl Ester can be incorporated into novel drug delivery systems to enhance its bioavailability and therapeutic outcomes. By employing various organic and metallic nanoparticles as carriers, the delivery, efficacy, and targeting of LTA4 to specific cells or tissues can be improved, potentially leading to more effective treatments for conditions related to leukotriene dysregulation.

Synthetic route

<(Z)-3-nonenyl>triphenyl phosphonium tosylate (82393-41-7) + (5S,6S)-epoxy-10-formyl-(7E,9E)-decadienoic acid methyl ester (73958-00-6) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
With n-butyllithium In tetrahydrofuran at -78℃;	90%

(5S,6S)-epoxy-10-formyl-(7E,9E)-decadienoic acid methyl ester (73958-00-6) + Phosphorane of (Z)-3-nonen-1-yl-triphenylphosponium bromide (73958-09-5) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at -78℃;	88%

<(3Z)-nonen-1-yl>triphenylphosphonium iodide (72297-07-5) + (5S,6S)-epoxy-10-formyl-(7E,9E)-decadienoic acid methyl ester (73958-00-6) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25h; Wittig reaction;	63%
With n-butyllithium In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide
With n-butyllithium 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min; Yield given. Multistep reaction;

(S)-5-hydroperoxy-6-trans,8,11,14-cis-eicosatetraenoic acid methyl ester (75331-81-6) → Leukotriene A4 methyl ester (73466-12-3) + methyl (6E,8Z,11Z,14Z)-5-oxo-6,8,11,14-eicosatetraenoate (74785-00-5)

Conditions	Yield
With 1,2,2,6,6-pentamethylpiperidine; trifluoromethanesulfonic acid anhydride In diethyl ether; dichloromethane at -110℃; for 0.666667h;	A 25% B n/a

diazomethane (186581-53-3, 908094-01-9) + 6-epi-Leukotriene A4 (71548-17-9, 72059-45-1, 74497-09-9, 76375-76-3, 77341-35-6, 114129-55-4, 114129-56-5, 114129-57-6) → Leukotriene A4 methyl ester (73466-12-3) + 5S,6R-6-epi-Leukotriene A4 methyl ester (76738-49-3) + 5R,6S-6-epi-Leukotriene A4 methyl ester (79356-68-6) + 5-epi-6-epi-leukotriene A4 methyl ester (79356-65-3)

Conditions	Yield
In diethyl ether at 0℃; for 0.166667h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

methyl 5(S),6(S)-oxido-11-oxo-7-cis-9-trans-undecadienoate (82442-92-0) + Phosphorane of (Z)-3-nonen-1-yl-triphenylphosponium bromide (73958-09-5) → Leukotriene A4 methyl ester (73466-12-3) + 7-cis-leukotriene A4 methyl ester (82467-14-9)

Conditions	Yield
In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at -78℃; for 0.333333h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(5S,6S)-epoxy-10-formyl-(7E,9E)-decadienoic acid methyl ester (73958-00-6) + triphenyl <(Z)-non-3-en-1-yl>phosphonium chloride (75415-25-7) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Yield given;

(5S,6S)-epoxy-11,14-eicosadiyne-7E,9E-dienoate (118333-88-3) → Leukotriene A4 methyl ester (73466-12-3) + 13,14-dehydro-leukotriene A4 methyl ester (82850-12-2) + 4-[(2S,3S)-((1E,3E,8Z)-3-Tetradeca-1,3,8-trien-5-ynyl)-oxiranyl]-butyric acid methyl ester (118333-83-8)

Conditions	Yield
With pyridine; hydrogen; Lindlar's catalyst In hexane at 20℃; under 750.06 Torr; Yields of byproduct given;	A 5.5 mg B n/a C n/a
With pyridine; hydrogen; Lindlar's catalyst In hexane at 20℃; under 750.06 Torr; Yield given;	A 5.5 mg B n/a C n/a

(-)-(S,S-trans)-3-(hydroxymethyl)oxiranebutanoic acid methyl ester (73957-99-0) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 68 percent / Py2*CrO3; 4 Angstroem molecular sieves / CH2Cl2 2: CH2Cl2 / 15 h 3: I2 / CH2Cl2 / 1 h 4: 63 percent / nBuLi; HMPA / tetrahydrofuran; hexane / 0.25 h / -78 °C View Scheme
Multi-step reaction with 3 steps 1: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 2: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 3: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 3 steps 1: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 2: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 3: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 3 steps 1: 63 percent / CrO3/Py / CH2Cl2 2: 70 percent 3: 90 percent / n-BuLi / tetrahydrofuran / -78 °C View Scheme
Multi-step reaction with 3 steps 1: 50 percent / Collins oxidation View Scheme

(+)-(S,R-trans)-3-formyloxiranebutanoic acid methyl ester (73427-12-0) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: CH2Cl2 / 15 h 2: I2 / CH2Cl2 / 1 h 3: 63 percent / nBuLi; HMPA / tetrahydrofuran; hexane / 0.25 h / -78 °C View Scheme
Multi-step reaction with 2 steps 1: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 2: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 2 steps 1: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 2: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

7-acetoxy-(5S,6S)-epoxyheptanoic acid methyl ester (76871-82-4) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 69 percent / K2CO3; Na2SO4 / methanol / 0.17 h / 20 °C 2: 68 percent / Py2*CrO3; 4 Angstroem molecular sieves / CH2Cl2 3: CH2Cl2 / 15 h 4: I2 / CH2Cl2 / 1 h 5: 63 percent / nBuLi; HMPA / tetrahydrofuran; hexane / 0.25 h / -78 °C View Scheme

(5S,6S)-epoxy-10-formyl-(9E)-decadienoic acid methyl ester (73958-00-6, 76738-48-2, 77341-38-9, 79356-64-2, 79356-67-5, 82442-92-0, 92009-26-2) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: I2 / CH2Cl2 / 1 h 2: 63 percent / nBuLi; HMPA / tetrahydrofuran; hexane / 0.25 h / -78 °C View Scheme
Multi-step reaction with 2 steps 1: iodine 2: BuLi / tetrahydrofuran; hexamethylphosphoric acid triamide View Scheme

7-acetoxy-(5S,6S)-epoxyheptanoic acid → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: diethyl ether / 0.08 h / 0 °C 2: 69 percent / K2CO3; Na2SO4 / methanol / 0.17 h / 20 °C 3: 68 percent / Py2*CrO3; 4 Angstroem molecular sieves / CH2Cl2 4: CH2Cl2 / 15 h 5: I2 / CH2Cl2 / 1 h 6: 63 percent / nBuLi; HMPA / tetrahydrofuran; hexane / 0.25 h / -78 °C View Scheme

3-nonyn-1-ol (31333-13-8) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 96.4 percent / hydrogen, quinoline / Lindlar catalyst / hexane / 1.25 h 2: 97.1 percent / pyridine / 1.5 h / 0 - 5 °C 3: 95 percent / sodium iodide / acetone / 67 h / Ambient temperature 4: 11.2 g / benzene / 43 h / 80 °C 5: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(Z)-non-3-en-1-ol (10340-23-5) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 97.1 percent / pyridine / 1.5 h / 0 - 5 °C 2: 95 percent / sodium iodide / acetone / 67 h / Ambient temperature 3: 11.2 g / benzene / 43 h / 80 °C 4: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

[(4R,5S)-5-((Z)-3-[1,3]Dioxan-2-yl-propenyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol (85612-85-7) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 9 steps 1: 40.8 g / pyridine / 3 h / 5 °C 2: 100 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 3: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 4: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 5: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 6: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 7: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 8: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 9: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 9 steps 1: 40.8 g / pyridine / 3 h / 5 °C 2: 100 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 3: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 4: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 5: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 6: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 7: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 8: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 9: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

3-cis-nonene-1-yl-p-toluenesulfonate (72297-08-6) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / sodium iodide / acetone / 67 h / Ambient temperature 2: 11.2 g / benzene / 43 h / 80 °C 3: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(1’R)-(-)-4,6-O-ethylidene-D-glucose (13224-97-0, 13224-98-1, 13224-99-2, 13225-00-8, 13225-01-9, 13225-02-0, 18465-50-4, 87068-63-1) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 10 steps 1: NaIO4, aq. sodium hydroxide / H2O / 0.25 h / 5 - 10 °C / pH 4 2: 4.7 g / tetrahydrofuran / 0.33 h / -30 °C 3: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 4: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 5: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 6: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 7: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 8: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 9: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 10: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 10 steps 1: NaIO4, aq. sodium hydroxide / H2O / 0.25 h / 5 - 10 °C / pH 4 2: 4.7 g / tetrahydrofuran / 0.33 h / -30 °C 3: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 4: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 5: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 6: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 7: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 8: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 9: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 10: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(+)--6-<2-<(benzoyloxy)-1-hydroxy>ethyl>tetrahydro-2H-pyran-2-one (77332-97-9) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 2: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 3: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 4: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 5: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 5 steps 1: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 2: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 3: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 4: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 5: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

Benzoic acid (R)-2-methanesulfonyloxy-2-((S)-6-oxo-tetrahydro-pyran-2-yl)-ethyl ester (77332-98-0) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 2: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 3: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 4: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 4 steps 1: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 2: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 3: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 4: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(+)-(4S-cis)-2,2-dimethyl-5-<(benzoyloxy)methyl>-1,3-dioxolane-4-butanoic acid 3-hydroxypropyl ester (77333-01-8) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 2: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 3: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 4: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 5: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 6: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 6 steps 1: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 2: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 3: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 4: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 5: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 6: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(+)-(4R-cis)-2,2-dimethyl-5-<3-(1,3-dioxan-2-yl)-1-propyl>-1,3-dioxolane-4-methanol benzoate (77333-00-7, 85648-04-0) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 2: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 3: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 4: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 5: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 6: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 7: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 7 steps 1: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 2: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 3: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 4: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 5: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 6: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 7: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(+)-(4R-cis)(Z)-2,2-dimethyl-5-<3-(1,3-dioxan-2-yl)-1-propenyl>-1,3-dioxolane-4-methanol benzoate (77332-94-6, 77398-80-2) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 8 steps 1: 100 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 2: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 3: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 4: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 5: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 6: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 7: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 8: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 8 steps 1: 100 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 2: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 3: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 4: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 5: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 6: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 7: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 8: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(3Z)-3-nonenyliodide (72297-09-7) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 11.2 g / benzene / 43 h / 80 °C 2: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(2R,4S,5R)-4-((E)-3-[1,3]Dioxan-2-yl-propenyl)-2-methyl-[1,3]dioxan-5-ol (85612-90-4) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 8 steps 1: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 2: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 3: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 4: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 5: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 6: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 7: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 8: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 8 steps 1: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 2: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 3: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 4: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 5: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 6: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 7: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 8: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

Methanesulfonic acid (R)-2-hydroxy-1-((S)-6-oxo-tetrahydro-pyran-2-yl)-ethyl ester (85612-93-7) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 2: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 3: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 4: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 4 steps 1: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 2: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 3: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 4: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(-)-(2R,4S,5R)-4-<3-(1,3-dioxan-2-yl)propyl>-2-methyl-1,3-dioxan-5-ol methanesulfonate (85612-91-5) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 2: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 3: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 4: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 5: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 6: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 6 steps 1: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 2: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 3: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 4: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 5: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 6: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(2R,4S,5R)(E)-4-<3-(1,3-dioxan-2-yl)-1-propenyl>-2-methyl-1,3-dioxan-5-ol methanesulfonate (85612-89-1) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 2: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 3: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 4: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 5: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 6: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 7: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 7 steps 1: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 2: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 3: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 4: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 5: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 6: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 7: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(-)-(2R,4S,5R)-2-methyl-5-<(methylsulfonyl)oxy>-1,3-dioxane-4-butanoic acid 3-hydroxypropyl ester (85612-92-6) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 2: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 3: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 4: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 5: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 5 steps 1: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 2: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 3: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 4: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 5: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(1'R)-(-)-2,4-O-ethylidene-D-erythrose (70377-89-8) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 9 steps 1: 4.7 g / tetrahydrofuran / 0.33 h / -30 °C 2: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 3: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 4: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 5: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 6: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 7: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 8: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 9: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 9 steps 1: 4.7 g / tetrahydrofuran / 0.33 h / -30 °C 2: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 3: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 4: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 5: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 6: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 7: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 8: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 9: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

L-cysteine methyl ester hydrochloride (18598-63-5) + Leukotriene A4 methyl ester (73466-12-3) → leukotriene E4 dimethyl ester (74448-22-9)

Conditions	Yield
With triethylamine In methanol; water for 1h; Ambient temperature; pH 9;	94%
With triethylamine In methanol for 5h; Ring cleavage; Condensation;	75%

Leukotriene A4 methyl ester (73466-12-3) + N-(trifluoroacetyl)-L-cysteinylglycine methyl ester (75290-62-9) → N-trifluoroacetyl-leukotriene D4 dimethyl ester (76322-44-6)

Conditions	Yield
With triethylamine In methanol for 4h; Ring cleavage; Condensation;	77%

Leukotriene A4 methyl ester (73466-12-3) + methyl 6-mercapto-3(E)-hexenoate (135388-27-1) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-((E)-5-methoxycarbonyl-pent-3-enylsulfanyl)-icosa-7,9,11,14-tetraenoic acid methyl ester (140215-33-4)

Conditions	Yield
With sodium methylate In methanol for 3h; Ambient temperature;	71%

Oxidized glutathione (27025-41-8) + Leukotriene A4 methyl ester (73466-12-3) → Leukotriene C4 methyl ester (73958-10-8)

Conditions	Yield
With triethylamine In methanol for 12h; Condensation; Ring cleavage;	55%

GLUTATHIONE (70-18-8) + Leukotriene A4 methyl ester (73466-12-3) → (7E,9E,11Z,14Z)-(5S,6R)-6-[(R)-2-(4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester

Conditions	Yield
With triethylamine for 2h; Ambient temperature;

3-Dimethylaminopropanethiol (42302-17-0) + Leukotriene A4 methyl ester (73466-12-3) → (7E,9E,11Z,14Z)-(5S,6R)-6-(3-Dimethylamino-propylsulfanyl)-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester (83851-65-4)

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;

1-mercapto-5-carbomethoxy-pentane (20756-86-9) + Leukotriene A4 methyl ester (73466-12-3) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-(5-methoxycarbonyl-pentylsulfanyl)-icosa-7,9,11,14-tetraenoic acid methyl ester

Conditions	Yield
With sodium methylate In methanol

N-Trifluoroacetylglutathione dimethyl ester (75290-61-8) + Leukotriene A4 methyl ester (73466-12-3) → (6E,8E,10E,14Z)-(S)-5-Hydroxy-12-{(R)-2-(methoxycarbonylmethyl-carbamoyl)-2-[(R)-4-methoxycarbonyl-4-(2,2,2-trifluoro-acetylamino)-butyrylamino]-ethylsulfanyl}-icosa-6,8,10,14-tetraenoic acid methyl ester (76695-80-2, 76740-25-5)

Conditions	Yield
With lithium perchlorate In tetrahydrofuran; diethyl ether at 23℃; for 12h; Yield given;

Leukotriene A4 methyl ester (73466-12-3) + methyl 6-mercapto-3(Z)-hexenoate (140215-41-4) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-((Z)-5-methoxycarbonyl-pent-3-enylsulfanyl)-icosa-7,9,11,14-tetraenoic acid methyl ester (140215-33-4)

Conditions	Yield
With sodium methylate In methanol Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + (S)-4-((R)-2-Mercapto-1-methoxycarbonyl-ethylcarbamoyl)-2-(2,2,2-trifluoro-acetylamino)-butyric acid methyl ester (83851-50-7) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-{(R)-2-methoxycarbonyl-2-[(S)-4-methoxycarbonyl-4-(2,2,2-trifluoro-acetylamino)-butyrylamino]-ethylsulfanyl}-icosa-7,9,11,14-tetraenoic acid methyl ester (83851-62-1, 84414-54-0)

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + methyl 3-mercaptopropionylglycinate (80115-99-7) → deamino LTD4 dimethyl ester (80116-00-3)

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;	4.2 mg

Leukotriene A4 methyl ester (73466-12-3) + 3-mercaptopropionylglycinedimethylamide (83851-49-4) → (7E,9E,11Z,14Z)-(5S,6R)-6-[2-(Dimethylcarbamoylmethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;	2.3 mg

Leukotriene A4 methyl ester (73466-12-3) + [(3-Mercapto-propyl)-(2,2,2-trifluoro-acetyl)-amino]-acetic acid methyl ester (83851-52-9) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-{3-[methoxycarbonylmethyl-(2,2,2-trifluoro-acetyl)-amino]-propylsulfanyl}-icosa-7,9,11,14-tetraenoic acid methyl ester (83851-64-3)

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + 4-[(R)-2-Mercapto-1-(methoxycarbonylmethyl-carbamoyl)-ethylcarbamoyl]-butyric acid methyl ester (83851-48-3) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-[(R)-2-(4-methoxycarbonyl-butyrylamino)-2-(methoxycarbonylmethyl-carbamoyl)-ethylsulfanyl]-icosa-7,9,11,14-tetraenoic acid methyl ester

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + (S)-2-[(R)-3-Mercapto-2-(2,2,2-trifluoro-acetylamino)-propionylamino]-pentanedioic acid dimethyl ester (83851-51-8) → (S)-2-[(R)-3-[(2E,4E,6Z,9Z)-(R)-1-((S)-1-Hydroxy-4-methoxycarbonyl-butyl)-pentadeca-2,4,6,9-tetraenylsulfanyl]-2-(2,2,2-trifluoro-acetylamino)-propionylamino]-pentanedioic acid dimethyl ester (83851-63-2)

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + L-cysteinylglycine → (7E,9E,11Z,14Z)-(5S,6R)-6-[(R)-2-Amino-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester

Conditions	Yield
With triethylamine In methanol; water for 18h; Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + glutathione → (7E,9E,11Z,14Z)-(5S,6R)-6-[2-(4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester (73958-10-8, 74841-70-6, 84823-29-0, 84823-30-3, 89461-60-9, 89461-61-0, 89461-62-1, 89461-63-2, 92009-28-4, 113830-70-9, 113830-71-0, 113830-72-1)

Conditions	Yield
With triethylamine In methanol at 23℃; for 5h;

Leukotriene A4 methyl ester (73466-12-3) → leukotriene E4 (75715-89-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / Et3N / methanol / 5 h 2: 82 percent / K2CO3 / methanol; H2O / 3.5 h / 0 °C View Scheme

Leukotriene A4 methyl ester (73466-12-3) → leukotriene D4 (73836-78-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 77 percent / Et3N / methanol / 4 h 2: 82 percent / K2CO3 / methanol; H2O / 3.5 h / 0 °C View Scheme

Leukotriene A4 methyl ester (73466-12-3) → (7E,9E,11Z,14Z)-(5S,6R)-6-[(R)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid (73466-14-5, 74841-69-3, 76738-45-9, 79026-71-4, 79026-72-5, 80629-45-4, 82468-64-2, 84823-19-8, 84823-20-1, 87391-79-5, 92009-30-8, 92418-31-0, 92418-46-7, 72025-60-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 55 percent / Et3N / methanol / 12 h 2: 84 percent / K2CO3 / methanol; H2O / 3.5 h / 20 °C View Scheme

Upstream product

• 186581-53-3 diazomethane 
• 71548-17-9 6-epi-Leukotriene A₄ 
• 72297-07-5 <(3Z)-nonen-1-yl>triphenylphosphonium iodide 
• 73958-00-6 (5S,6S)-epoxy-10-formyl-(7E,9E)-decadienoic acid methyl ester 
• 82393-41-7 <(Z)-3-nonenyl>triphenyl phosphonium tosylate 
• 82442-92-0 methyl 5(S),6(S)-oxido-11-oxo-7-cis-9-trans-undecadienoate 
• 73958-09-5 Phosphorane of (Z)-3-nonen-1-yl-triphenylphosponium bromide 
• 75415-25-7 triphenyl <(Z)-non-3-en-1-yl>phosphonium chloride 
• 118333-88-3 (5S,6S)-epoxy-11,14-eicosadiyne-7E,9E-dienoate 
• 75331-81-6 (S)-5-hydroperoxy-6-trans,8,11,14-cis-eicosatetraenoic acid methyl ester 
• 73957-99-0 (-)-(S,S-trans)-3-(hydroxymethyl)oxiranebutanoic acid methyl ester 
• 73427-12-0 (+)-(S,R-trans)-3-formyloxiranebutanoic acid methyl ester 
• 76871-82-4 7-acetoxy-(5S,6S)-epoxyheptanoic acid methyl ester 
• 73958-00-6 (5S,6S)-epoxy-10-formyl-(9E)-decadienoic acid methyl ester 

Downstream Products

• 89461-64-3 7Z,9E,11E,14Z-LTE₄ methyl ester 
• 91944-21-7 7Z,9E,11E,14Z-LTD₄ methyl ester 
• 73958-10-8 (7E,9E,11Z,14Z)-(5S,6R)-6-[2-(4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester 
• 73466-14-5 (7E,9E,11Z,14Z)-(5S,6R)-6-[(R)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid 
• 79026-72-5 (5R,6S)-LTC₄ 
• 72025-60-6 (7E,9Z,11Z,14Z)-(5S,6R)-6-[(S)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid 
• 72025-60-6 (7E,9Z,11Z,14Z)-(5R,6S)-6-[(S)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid 
• 72025-60-6 5(S)-hydroxy-6(R)-glutathionyl-7,9-E-11,14-Z-eicosatetraenoic acid 
• 72025-60-6 leukotriene C4 
• 73958-10-8 (7E,9E,11Z,14Z)-(5S,6R)-6-[2-(4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester 
• 73958-10-8 Leukotriene C₄ methyl ester 
• 75715-89-8 leukotriene E4 
• 73836-78-9 leukotriene D4 
• 75443-89-9 7Z,9E,11E,14Z-LTE₄ 

Relevant articles and documents

Total synthesis of leukotrienes from butadiene

The total synthesis of leukotrienes has been achieved starting from butadiene by a palladium-catalyzed telomerization at room temperature. A Sharpless catalytic asymmetric epoxidation generated the asymmetric centers with >94% ee. Simple transformations of the key intermediate 15 produced the leukotrienes LTA4 methyl ester (4), LTC4 (1), LTD4 (2) and LTE4 (3), as well as (14S, 15S)-LTA4 methyl ester (24) and the novel [2H2]-LTA4 methyl ester (28). The use of the opposite chiral director in the Sharpless catalytic asymmetric epoxidation gave the key intermediate 15a that has been used in the synthesis of the double epimers of the leukotrienes as well as LTB4.

Synthesis of leukotriene A4 methyl ester from D-glucose

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A FACILE STEREOSELECTIVE SYNTHESIS OF LEUKOTRIENE A4(LTA4) METHYL ESTER

A facile synthesis of LTA4 1 methyl ester was achieved according to Scheme 1, in which the key intermediate 6 and 7 were prepared with the new procedures conveniently, stereoselectively and in good yields.