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【结 构 式】 
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【分子编号】53114 【品名】(1S,6S,11aS,13S,14aR)-1,13-dihydroxy-6-methyl-1,6,7,8,9,11a,12,13,14,14a-decahydro-4H-cyclopenta[f]oxacyclotridecin-4-one 【CA登记号】n/a |
【 分 子 式 】C16H24O4 【 分 子 量 】280.36416 【元素组成】C 68.55% H 8.63% O 22.83% |
合成路线1
该中间体在本合成路线中的序号：(I)Michael addition of 2-mercaptoethanol (II) to the unsaturated lactone function of (+)-brefeldin A (I) in the presence of Proton Sponge afforded the sulfanyl adduct (III). The title sulfoxide was then obtained by oxidation of sulfide (III) with meta-chloroperbenzoic acid.
| 【1】 Fox, B.M.; et al.; Design and synthesis of (+)-brefeldin A sulfide prodrugs with enhanced aqueous solubilities. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 97. |
| 【2】 Argade, A.B.; Devraj, R.; Vroman, J.A.; Haugwitz, R.D.; Hollingshead, M.; Cushman, M.; Design and synthesis of brefeldin A sulfide derivatives as prodrug candidates with enhanced aqueous solubilities. J Med Chem 1998, 41, 18, 3337. |
| 【3】 Cushman, M.S.; Devraj, R.; Argade, A.B.; Haughwitz, R.D. (Purdue Research Foundation); Brefeldin A derivs.. US 6362218; WO 9931084 . |
| 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) | 53114 | (1S,6S,11aS,13S,14aR)-1,13-dihydroxy-6-methyl-1,6,7,8,9,11a,12,13,14,14a-decahydro-4H-cyclopenta[f]oxacyclotridecin-4-one | n/a | C16H24O4 | 详情 | 详情 |
| (II) | 36375 | 2-Sulfanyl-1-ethanol; 2-Mercaptoethanol | 60-24-2 | C2H6OS | 详情 | 详情 |
| (III) | 53115 | (1S,2R,6S,11aS,13S,14aR)-1,13-dihydroxy-2-[(2-hydroxyethyl)sulfanyl]-6-methyl-1,2,3,6,7,8,9,11a,12,13,14,14a-dodecahydro-4H-cyclopenta[f]oxacyclotridecin-4-one | n/a | C18H30O5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The sulfide adduct (III) was obtained as a diastereomeric mixture by Michael addition of racemic 1-mercapto-2-propanol (II) to the unsaturated lactone function of brefeldin A (I) in the presence of proton sponge(R). Diastereoselective oxidation of sulfide (III) with m-CPBA produced the corresponding sulfoxide as a mixture of epimers at the C2' position, from which the title 2'S compound was isolated by means of flash chromatography.
| 【1】 Fox, B.M.; et al.; Preparation and evaluation of sulfide derivatives of the antibiotic brefeldin A as potential prodrug candidates with enhanced aqueous solubilities. J Med Chem 2001, 44, 23, 3915. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IIIa) | 53383 | (1S,2R,6S,11aS,13S)-1,13-dihydroxy-2-{[(2S)-2-hydroxypropyl]sulfanyl}-6-methyl-1,2,3,6,7,8,9,11a,12,13,14,14a-dodecahydro-4H-cyclopenta[f]oxacyclotridecin-4-one | n/a | C19H32O5S | 详情 | 详情 |
| (IIIb) | 53384 | (1S,2R,6S,11aS,13S)-1,13-dihydroxy-2-{[(2R)-2-hydroxypropyl]sulfanyl}-6-methyl-1,2,3,6,7,8,9,11a,12,13,14,14a-dodecahydro-4H-cyclopenta[f]oxacyclotridecin-4-one | n/a | C19H32O5S | 详情 | 详情 |
| (I) | 53114 | (1S,6S,11aS,13S,14aR)-1,13-dihydroxy-6-methyl-1,6,7,8,9,11a,12,13,14,14a-decahydro-4H-cyclopenta[f]oxacyclotridecin-4-one | n/a | C16H24O4 | 详情 | 详情 |
| (II) | 53382 | 1-Mercapto-2-propanol | 1068-47-9 | C3H8OS | 详情 | 详情 |