120205-58-5

Basic information

• Product Name: tert-Butyl (3R,4S,5S)-3-methoxy-4--5-methylheptanoate
• Synonyms: tert-Butyl (3R,4S,5S)-3-methoxy-4--5-methylheptanoate
• CAS NO: 120205-58-5
• Molecular Weight: 393.524
• Mol File: 120205-58-5.mol
• Article Data: 7

Chemical Properties

• CAS DataBase Reference: tert-Butyl (3R,4S,5S)-3-methoxy-4--5-methylheptanoate(CAS DataBase Reference)
• NIST Chemistry Reference: tert-Butyl (3R,4S,5S)-3-methoxy-4--5-methylheptanoate(120205-58-5)
• EPA Substance Registry System: tert-Butyl (3R,4S,5S)-3-methoxy-4--5-methylheptanoate(120205-58-5)

Safety Data

• Hazardous Substances Data: 120205-58-5(Hazardous Substances Data)

Upstream product

• 135383-55-0 (3R,4S,5S)-4-Benzyloxycarbonylamino-3-hydroxy-5-methyl-heptanoic acid tert-butyl ester 
• 333-27-7 methyl trifluoromethanesulfonate 
• 120294-43-1 tert-Butyl (3R,4S,5S)-3-hydroxy-4--5-methylheptanoate 
• 420-37-1 trimethoxonium tetrafluoroborate 
• 135383-54-9 (4S,5S)-4-Benzyloxycarbonylamino-5-methyl-3-oxo-heptanoic acid tert-butyl ester 
• 150942-98-6 t-butyl lithioacetate 
• 3160-59-6 N-Cbz-L-Isoleucine 
• 149664-79-9 (3R,4S,5S)-4-(Benzyloxycarbonyl-methyl-amino)-3-methoxy-5-methyl-heptanoic acid methyl ester 
• 135383-56-1 (3R,4S,5S)-4--3-methoxy-5-methylheptanoic acid 
• 115-11-7 isobutene 
• 120205-56-3 benzyl methyl[(2S,3S)-3-methyl-1-oxopentan-2-yl]carbamate 
• 42417-66-3 (2S,3S)-3-methyl-2-(methyl{[(phenylmethyl)oxy]carbonyl}amino)pentanoic acid 
• 120205-55-2 benzyl [(2S,3S)-1-hydroxy-3-methylpentan-2-yl]methylcarbamate 

Downstream Products

• 159173-45-2 (3R,4S,5S)-Dil-(2R,3R,4S)-Dap-(S)-Doe 
• 135383-61-8 Cbz-Dil-Dap-Doe 
• 135383-62-9 Boc-(S)-Val-(3R,4S,5S)-Dil-(2R,3R,4S)-Dap-(S)-Doe 
• 120205-48-3 tert-Butyl (3R,4S,5S)-3-methoxy-4-(N-methylamino)-5-methylheptanoate hydrochloride 
• 1438852-21-1 methyl (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-phenylpropanoate 
• 1438852-80-2 pentafluorophenyl (3R,4S,5S)-4-[{N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valyl}(methyl)amino]-3-methoxy-5-methylheptanoate 

Relevant articles and documents

Rational Design of Azastatin as a Potential ADC Payload with Reduced Bystander Killing

Auristatins are a class of ultrapotent microtubule inhibitors, whose growing clinical popularity in oncology is based upon their use as payloads in antibody-drug conjugates (ADCs). The most widely utilized auristatin, MMAE, has however been shown to cause apoptosis in non-pathological cells proximal to the tumour (“bystander killing”). Herein, we introduce azastatins, a new class of auristatin derivatives encompassing a side chain amine for antibody conjugation. The synthesis of Cbz-azastatin methyl ester, which included the C2-elongation and diastereoselective reduction of two proteinogenic amino acids as key transformations, was accomplished in 22 steps and 0.76 % overall yield. While Cbz-protected azastatin methyl ester (0.13–3.0 nM) inhibited proliferation more potently than MMAE (0.47–6.5 nM), removal of the Cbz-group yielded dramatically increased IC50-values (9.8–170 nM). We attribute the reduced apparent cytotoxicity of the deprotected azastatin methyl esters to a lack of membrane permeability. These results clearly establish the azastatins as a novel class of cytotoxic payloads ideally suited for use in next-generation ADC development.

CYTOTOXIC PEPTIDES AND ANTIBODY DRUG CONJUGATES THEREOF

The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.

Synthesis and antitumor activity of novel dolastatin 10 analogs

Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10 analogs each modified at one of the constituent amino acid derivatives, were synthesized and their antitumor activity was evaluated against P388 leukemia in mice. The structural requirements for antitumor activity are discussed. Some of the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly active 50c, which lacks the thiazole group of 1, was selected for further development as an antitumor agent.