benzyl (1S,2S)-1-formyl-2-methylbutyl(methyl)carbamate -Drug Synthesis Database

【结构式】

【分子编号】54629

【品名】benzyl (1S,2S)-1-formyl-2-methylbutyl(methyl)carbamate

【CA登记号】

【分子式】C₁₅H₂₁NO₃

【分子量】263.33668

【元素组成】C 68.42% H 8.04% N 5.32% O 18.23%

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：(IV)

The methylation of N-(benzyloxycarbonyl)-L-isoleucine (I) with Me-I and NaH in THF gives the N-methyl derivative (II), which is reduced with BH3 in THF to yield the isoleucinol (III). The oxidation of (III) with SO3/pyridine in DMSO affords the isoleucinal (IV), which is condensed with tert-butyl acetate (V) by means of BuLi and THF to afford the chiral beta-hydroxyheptanoate (VI). Finally, this compound is O-methylated by means of diazomethane and BF3 in ethyl ether/dichloromethane and N-deprotected by hydrogenation with H2 over Pd/C in ethyl acetate/methanol to provide the desired intermediate, the chiral tert-butyl heptanoate (VII).

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
(I)	23508	(2S,3S)-2-[[(benzyloxy)carbonyl]amino]-3-methylpentanoic acid	3160-59-6	C₁₄H₁₉NO₄	详情	详情
(II)	54627	(2S,3S)-2-[[(benzyloxy)carbonyl](methyl)amino]-3-methylpentanoic acid		C₁₅H₂₁NO₄	详情	详情
(III)	54628	benzyl (1S,2S)-1-(hydroxymethyl)-2-methylbutyl(methyl)carbamate		C₁₅H₂₃NO₃	详情	详情
(IV)	54629	benzyl (1S,2S)-1-formyl-2-methylbutyl(methyl)carbamate		C₁₅H₂₁NO₃	详情	详情
(V)	13597	2,2-Dimethylpropanoyl chloride; Pivaloyl chloride	3282-30-2	C₅H₉ClO	详情	详情
(VI)	54630	tert-butyl (3R,4S,5S)-4-[[(benzyloxy)carbonyl](methyl)amino]-3-hydroxy-5-methylheptanoate		C₂₁H₃₃NO₅	详情	详情
(VII)	23514	tert-butyl (3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoate		C₁₄H₂₉NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

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