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【结 构 式】 
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【分子编号】53768 【品名】(2S)-2-[(1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl]propyl phenyl sulfone; {(2S)-2-[(1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl]propyl}(dioxo)phenyl-lambda~6~-sulfane 【CA登记号】n/a |
【 分 子 式 】C29H42O3S 【 分 子 量 】470.71668 【元素组成】C 74% H 8.99% O 10.2% S 6.81% |
合成路线1
该中间体在本合成路线中的序号：(LXXXVIII)A stereoselective synthesis of the (24R)-epimer of squalamine dessulfate (CIII) has been reported starting from stigmasterol (LXXXII). Tosylate (LXXXIII) prepared from (LXXXII) was rearranged in the presence of potassium acetate in methanol to afford the cyclopropane compound (LXXXIV). Ozonization of the double bond produced aldehyde (LXXXV), which was subsequently reduced to alcohol (LXXXVI) by means of NaBH4. The primary alcohol (LXXXVI) was converted into the corresponding mesylate, which was further displaced by NaI to provide the alkyl iodide (LXXXVII). Condensation of iodide (LXXXVII) with sodium benzenesulfinate furnished sulfone (LXXXVIII).
| 【1】 Moriarty, R.M.; et al.; Stereoselective synthesis of squalamine dessulfate. Tetrahedron Lett 1995, 36, 29, 5139. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LXXXII) | 53762 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R,2E,4S)-4-ethyl-1,5-dimethyl-2-hexenyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol | n/a | C29H48O | 详情 | 详情 |
| (LXXXIII) | 53763 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R,2E,4S)-4-ethyl-1,5-dimethyl-2-hexenyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-methylbenzenesulfonate | n/a | C36H54O3S | 详情 | 详情 |
| (LXXXIV) | 53764 | (1aR,3aR,3bS,5aR,6R,8aS,8bS,10R,10aR)-6-[(1R,2E,4S)-4-ethyl-1,5-dimethyl-2-hexenyl]-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-10-yl methyl ether; (1aR,3aR,3bS,5aR,6R,8aS,8bS,10R,10aR)-6-[(1R,2E,4S)-4-ethyl-1,5-dimethyl-2-hexenyl]-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalene | n/a | C30H50O | 详情 | 详情 |
| (LXXXV) | 53765 | (2S)-2-[(1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl]propanal | n/a | C23H36O2 | 详情 | 详情 |
| (LXXXVI) | 53766 | (2S)-2-[(1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl]-1-propanol | n/a | C23H38O2 | 详情 | 详情 |
| (LXXXVII) | 53767 | (1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-6-[(1S)-2-iodo-1-methylethyl]-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-10-yl methyl ether; (1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-6-[(1S)-2-iodo-1-methylethyl]-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalene | n/a | C23H37IO | 详情 | 详情 |
| (LXXXVIII) | 53768 | (2S)-2-[(1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl]propyl phenyl sulfone; {(2S)-2-[(1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl]propyl}(dioxo)phenyl-lambda~6~-sulfane | n/a | C29H42O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LXXXVII)Diazotization of (S)-valine (LXXXIX) gave rise to the alpha-hydroxyacid (XC), which was reduced to diol (XCI) using LiAlH4. Tosylation of the primary hydroxyl of (XCI), followed by cyclization of the resulting tosylate (XCII) under basic conditions, furnished epoxide (XCIII). Condensation of epoxide (XCIII) with the lithium anion derived from sulfone (LXXXVIII) gave adduct (XCIV). Reductive elimination of the phenylsulfonyl group and then acidic rearrangement of the cyclopropane ring provided the dihydroxy steroid (XCV). After protection of (XCV) as the diacetate (XCVI), allylic oxidation with CrO3 in the presence of dimethylpyrazole yielded enone (XCVII).
| 【1】 Moriarty, R.M.; et al.; Stereoselective synthesis of squalamine dessulfate. Tetrahedron Lett 1995, 36, 29, 5139. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LXXXVII) | 53768 | (2S)-2-[(1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl]propyl phenyl sulfone; {(2S)-2-[(1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl]propyl}(dioxo)phenyl-lambda~6~-sulfane | n/a | C29H42O3S | 详情 | 详情 |
| (LXXXIX) | 37828 | L-2-Amino-3-methylbutyric acid; L-2-Aminoisovaleric acid; 2-Aminoisovaleric acid; L-2-Amino-3-methylbutyric acid; L-alpha-Aminoisovaleric acid; L-valine; (S)-(+)-Valine; (S)-alpha-Aminoisovaleric acid | 72-18-4 | C5H11NO2 | 详情 | 详情 |
| (XC) | 37829 | (2S)-2-hydroxy-3-methylbutyric acid | C5H10O3 | 详情 | 详情 | |
| (XCI) | 53769 | (2S)-3-methyl-1,2-butanediol | n/a | C5H12O2 | 详情 | 详情 |
| (XCII) | 53770 | (2S)-2-hydroxy-3-methylbutyl 4-methylbenzenesulfonate | n/a | C12H18O4S | 详情 | 详情 |
| (XCIII) | 53771 | (2S)-2-isopropyloxirane | 123731-68-0 | C5H10O | 详情 | 详情 |
| (XCIV) | 53772 | (3R,6S)-6-[(1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-10-methoxy-3a,5a-dimethylhexadecahydrocyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl]-2-methyl-5-(phenylsulfonyl)-3-heptanol | n/a | C34H52O4S | 详情 | 详情 |
| (XCV) | 53773 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol | n/a | C27H46O2 | 详情 | 详情 |
| (XCVI) | 53774 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R,4R)-4-(acetyloxy)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C31H50O4 | 详情 | 详情 |
| (XCVII) | 53775 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R,4R)-4-(acetyloxy)-1,5-dimethylhexyl]-10,13-dimethyl-7-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C31H48O5 | 详情 | 详情 |