104121-92-8 Usage
Description
2-(3-hydroxypropoxy)-1,25-dihydroxyvitamin D3, also known as Eldecalcitol or Edirol, is a synthetic derivative of vitamin D3. It is characterized by the presence of a 3-hydroxypropoxy group at position 2 of the calcitriol molecule. Eldecalcitol was approved in January 2011 by the Japanese Ministry of Health, Labor, and Welfare for the treatment of osteoporosis. 2-(3-hydroxypropoxy)-1,25-dihydroxyvitamin D3 plays a crucial role in bone health by mediating intestinal calcium absorption, bone calcium metabolism, and potentially muscle activity.
Uses
Used in Pharmaceutical Industry:
2-(3-hydroxypropoxy)-1,25-dihydroxyvitamin D3 is used as a therapeutic agent for the treatment of osteoporosis. Its application is based on its ability to bind to the vitamin D receptor 2.7-fold more potently than calcitriol, while only weakly inhibiting serum parathyroid hormone. This makes it an effective treatment for patients diagnosed with osteoporosis, as it helps maintain bone health and density.
Used in Bone Health Applications:
In the field of bone health, 2-(3-hydroxypropoxy)-1,25-dihydroxyvitamin D3 is used to improve bone calcium metabolism and support overall bone health. Its role in mediating intestinal calcium absorption and potentially muscle activity contributes to its effectiveness in maintaining and improving bone health.
Used in Research and Development:
Eldecalcitol is also utilized in research and development for the study of vitamin D and its analogs. Its unique properties and potent binding to the vitamin D receptor make it a valuable compound for investigating the mechanisms of action and potential applications of vitamin D in various health conditions.
Originator
Chugai Pharmaceutical/Roche (Japan)
Clinical Use
Eldecalcitol is a vitamin D3 analog approved in Japan for the
treatment of osteoporosis. Itwasdiscoveredby Chugai and co-developed
with Taisho. Eldecalcitol, a hormonally active calcitrol analog,
regulates calcium and bone metabolism. The drug was approved on
the basis of results from randomized, double-blinded, parallelgroup,
phase III studies taking place over three years that showed
eldecalcitol to significantly lower incidence of new vertebral fractures
compared to those receiving the comparator drug alfacalcidol. Discovery and SAR studies of vitamin D3 analogs leading
to the identification of eldecalcitol have been reported. In
addition, multiple syntheses, including parallel approaches, have
been reported in publications and patents.
Synthesis
The biomimetic vitamin D3 analog synthesis that was recently disclosed, based on an
earlier reported route for the commercial synthesis of alfacalcidol,
will be discussed here.An Oppenauer oxidation converted commercially available cholesterol
141 to enone 142 in 80% yield. A second oxidation event
with DDQ provided dienone 143 in 75% yield. Treatment of 143
with sodium ethoxide in ethanol triggered migration of the enone
double bond into the B-ring, giving olefin 144 in 53% yield. Stereospecific
reduction of ketone 144 with sodium borohydride gave
alcohol 145 in 53% yield, which was then immediately protected
as the corresponding acetate with acetic anhydride to furnish
146. Next, further dehydrogenation of the B-ring was accomplished
using radical bromination of the olefin within 146 through
the use of NBS and catalytic AIBN, followed by elimination with
collidine. A subsequent saponification step ultimately gave rise to
the key diene 147. Next, in order to selectively epoxidize the A-ring
olefin, a unique ‘protection’ strategy was employed using phenyl-
1,2,4-triazole-3,5-dione (PTAD). Diels–Alder reaction between
diene 147 and PTAD produced cycloadduct 148 in 80% overall yield
from acetate 146. Protection of the alcohol as the corresponding
TBS ether preceeded a regio- and stereospecific epoxidation with
m-CPBA to afford 1,2a-epoxide 150 in 78% yield. Diels–Alder adduct
150 was then subjected to thermal conditions to affect a retro-[
4+2] reaction to give diene 151. Fluoride-mediated removal
of the TBS group prepared 3b-alcohol 152 in 95% yield. Subsequent
ring-opening reaction with 1,3-propane diol in the presence of
potassium t-butoxide, provided 3-hydroxy propoxy ether 153 in
29% yield. Microbial oxidation of intermediate 153 was accomplished
using an Amycolata autotrophica ATCC 33796 culture to obtain
eldecalcitol derivative 154 in 64% yield. Subjection of 154 to
400 watt light followed by thermolysis provided eldecalcitol (XII)
in 29% yield.
Check Digit Verification of cas no
The CAS Registry Mumber 104121-92-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,4,1,2 and 1 respectively; the second part has 2 digits, 9 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 104121-92:
(8*1)+(7*0)+(6*4)+(5*1)+(4*2)+(3*1)+(2*9)+(1*2)=68
68 % 10 = 8
So 104121-92-8 is a valid CAS Registry Number.
InChI:InChI=1/C30H50O5/c1-20(9-6-15-29(3,4)34)24-13-14-25-22(10-7-16-30(24,25)5)11-12-23-19-26(32)28(27(33)21(23)2)35-18-8-17-31/h11-12,20,24-28,31-34H,2,6-10,13-19H2,1,3-5H3/b22-11+,23-12-/t20-,24-,25+,26+,27+,28+,30-/m1/s1
104121-92-8Relevant articles and documents
Large-Scale Synthesis of Eldecalcitol
Moon, Hyung Wook,Lee, Seung Jong,Park, Seong Hu,Jung, Se Gyo,Jung, In A.,Seol, Chang Hun,Kim, Seung Woo,Lee, Seon Mi,Gangganna, Bogonda,Park, Seokhwi,Lee, Kee-Young,Oh, Chang-Young,Song, Juyoung,Jung, Jaehun,Heo, Ji Soo,Lee, Kang Hee,Kim, Hae Sol,Lee, Won Taek,Baek, Areum,Shin, Hyunik
, p. 98 - 107 (2021/01/09)
Industrial-scale synthesis of eldecalcitol is described. AA highly diastereoselective epoxidation of p-methoxybenzyl (PMB) protected dienol at room temperature provides the key epoxide intermediate with a secondary hydroxyl group, which is alkylated with a triflate to set up all of the subunits at the C-1, C-2, and C-3 positions of the A-ring fragment. Selective protecting group manipulation followed by palladium-catalyzed cyclization then provides the A-ring synthon. The C/D-ring fragment is obtained by (1) direct C-H hydroxylation of Grundman's ketone using in situ prepared trifluoropropanone dioxirane and (2) protection. Finally, the coupling of the A-ring with the C/D-ring fragment, global deprotection, and recrystallization provide the highly crystalline eldecalcitol.
NOVEL CRYSTAL FORM OF VITAMIN D3 DERIVATIVE AND METHOD FOR PRODUCING THE SAME
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Paragraph 0037, (2018/04/12)
PROBLEM TO BE SOLVED: To provide a novel crystal form of a vitamin D3 derivative and a method of producing the same. SOLUTION: The present invention provides a production method including crystallizing 1α,25-dihydroxy-2β-(3-hydroxypropoxy) vitamin D3 (compound (1)), known a vitamin D3 derivative, by quenching from a hydrous organic solvent, and further heating it, to obtain C crystals of the compound (1), and a crystalline form obtained as a result of it. SELECTED DRAWING: Figure 5 COPYRIGHT: (C)2018,JPOandINPIT
Two convergent approaches to the synthesis of 1,25-dihydroxy 2-(3-hydroxypropoxy)vitamin D3 (ED-71) by the lythgoe and thf trost coupling reactions
Maeyama, Junji,Hiyamizu, Hiroko,Takahashi, Keisuke,Ishihara, Jun,Hatakeyama, Susumi,Kubodera, Noboru
, p. 295 - 307 (2008/04/18)
Two convergent syntheses of 1,25-dihydroxy-2-(3-hydroxypropoxy)vitamin D3 (ED-71) by the Lythgoe coupling reaction between the A-ring phosphine oxide and the C/D-ring ketone and the Trost coupling reaction between the A-ring ene-yne and the C/D-ring bromomethylene are described.