(1S)-2-hydroxy-1,2,2-triphenylethyl propionate -Drug Synthesis Database

【结构式】

【分子编号】54631

【品名】(1S)-2-hydroxy-1,2,2-triphenylethyl propionate

【CA登记号】

【分子式】C₂₃H₂₂O₃

【分子量】346.42588

【元素组成】C 79.74% H 6.4% O 13.86%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XI)

The reaction of L-prolinol (VIII) with Boc2O gives N-Boc-L-prolinol (IX), which is oxidized with SO3/pyridine in DMSO to afford N-Boc-L-prolinal (X). The condensation of (X) with the propionate ester (XI), by means of LDA in THF, affords the 3-hydroxy-3-(2-pyrrolidinyl)propionate ester (XII), which is methylated with diazomethane and BF3 in dichloromethane to provide the corresponding methoxy derivative (XIII). The epimerization of the (S)-methyl group of group of (XIII) by means of t-Bu-OK in THF gives the corresponding (R)-methyl derivative (XIV), which is finally hydrogenolyzed with H2 over Pd/C in ethyl acetate/methanol to yield the desired pyrrolidinylpropionic acid intermediate (XV).

参考文献中间体

合成目标

【1】 Pettit, G.R.; Singh, S.B.; Williams, M.D.; Herald, D.L.; Hogan, F.; Burkett, D.D.; Clewlow, P.J.; The absolute configuration and synthesis of natural (-)-Dolastatin 10. J Am Chem Soc 1989, 111, Suppl. 3, 5463.
【2】 Pettit, G.R.; Srirangam, J.K.; Singh, S.B.; Williams, M.D.; Herald, D.L.; Barkóczy, J.; Kantoci, D.; Hogan, F.; Dolastatins 24. Synthesis of (-)-dolastatin 10. X-Ray molecular structure of N,N-dimethylvalyl-valyl-dolaisoleucine tert-butyl ester. J Chem Soc Perkins Trans I 1996, 8, Suppl. 3, 859-63.
【3】 Pettit, G.R.; Singh, S.B. (Arizona State University); Synthesis of dolastatin 10. US 4978744 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	21347	(2S)pyrrolidinylmethanol	23356-96-9	C₅H₁₁NO	详情	详情
(IX)	49819	(S)-1-(tert-Butoxycarbonyl)-2-pyrrolidinenemethanol		C₁₀H₁₉NO₃	详情	详情
(X)	16724	tert-Butyl (2S)-2-formyltetrahydro-1H-pyrrole-1-carboxylate; tert-Butoxycarbonyl-L-prolinal	69610-41-9	C₁₀H₁₇NO₃	详情	详情
(XI)	54631	(1S)-2-hydroxy-1,2,2-triphenylethyl propionate		C₂₃H₂₂O₃	详情	详情
(XII)	54632	tert-butyl (2S)-2-((1R,2S)-1-hydroxy-3-{[(1S)-2-hydroxy-1,2,2-triphenylethyl]oxy}-2-methyl-3-oxopropyl)-1-pyrrolidinecarboxylate		C₃₃H₃₉NO₆	详情	详情
(XIII)	54633	tert-butyl (2S)-2-((1R,2S)-3-{[(1S)-2-hydroxy-1,2,2-triphenylethyl]oxy}-1-methoxy-2-methyl-3-oxopropyl)-1-pyrrolidinecarboxylate		C₃₄H₄₁NO₆	详情	详情
(XIV)	54634	tert-butyl (2S)-2-((1R,2R)-3-{[(1S)-2-hydroxy-1,2,2-triphenylethyl]oxy}-1-methoxy-2-methyl-3-oxopropyl)-1-pyrrolidinecarboxylate		C₃₄H₄₁NO₆	详情	详情
(XV)	23520	(2R,3R)-3-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]-3-methoxy-2-methylpropionic acid		C₁₄H₂₅NO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Coupling of diamine (IX) with the Boc-protected diamino acid (X) by means of DCC and HOBt gives rise to amide (XI). The title compound is finally obtained by acidic cleavage of the N-Boc protecting groups of (XI).

参考文献中间体

合成目标

【1】 Roberts, C.; et al.; Discovery af a new class of broad-spectrum antifungal compounds that target the minor groove of DNA. 28th Natl Med Chem Symp (June 8 2002, San Diego) 2002, Abst 67.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IX)	54629	benzyl (1S,2S)-1-formyl-2-methylbutyl(methyl)carbamate	C₁₅H₂₁NO₃	详情	详情
(X)	54630	tert-butyl (3R,4S,5S)-4-[[(benzyloxy)carbonyl](methyl)amino]-3-hydroxy-5-methylheptanoate	C₂₁H₃₃NO₅	详情	详情
(XI)	54631	(1S)-2-hydroxy-1,2,2-triphenylethyl propionate	C₂₃H₂₂O₃	详情	详情

Extended Information