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【结 构 式】 
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【药物名称】Olivomycin A 【化学名称】(2S,3S)-6-[4-O-Acetyl-2,6-dideoxy-3-O-(2,6-dideoxy-4-O-methyl-alpha-D-galactopyranosyl)-beta-D-galactopyranosyloxy]-2-[2,6-dideoxy-3-O-[2,6-dideoxy-3-O-(2,6-dideoxy-4-O-isobutyryl-3-C-methyl-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl]-beta-D-glucopyranosyloxy]-3-[3(S),4(R)-dihydroxy-1(S)-methoxy-2-oxopentyl]-8,9-dihydroxy-1,2,3,4-tetrahydroanthracen-1-one 【CA登记号】6988-58-5 【 分 子 式 】C58H84O26 【 分 子 量 】1197.30058 |
【开发单位】Shionogi (Not Determined) 【药理作用】Antibiotics and Alkaloids, Antineoplastic Antibiotics, ONCOLYTIC DRUGS |
合成路线1
The condensation of the protected aglucone (I) with the glucoside (II) by means of TBS triflate gives the condensed alpha-glucoside (III), which is worked up to yield the bis-chloroacetylated intermediate that is desilylated to compound (IV). The condensation of (IV) with disaccharide (V) gives the trisaccharide (VI), which by deprotection of the phenolic chloroacetate and condensation with disaccharide (VII) affords the pentasaccharide (VIII).
| 【1】 Roush, W.R.; et al.; Total synthesis of olivomycin A. J Am Chem Soc 1999, 121, 9, 1990. |
| 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) | 26399 | (3R)-8-[(benzyloxy)methoxy]-6,9-bis[(E)-2-butenyloxy]-2-hydroxy-3-[(1S)-1-methoxy-2-[(2R,3R)-3-methyl-1,4-dioxaspiro[4.4]non-2-yl]-2-oxoethyl]-3,4-dihydro-1(2H)-anthracenone | C41H48O10 | 详情 | 详情 | |
| (II) | 26400 | (2S,3R,4S,5R,6R)-2-(bromomethyl)-5-(phenylsulfanyl)-6-[(2,2,2-trichloroethanimidoyl)oxy]-4-[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 2-chloroacetate | C22H30BrCl4NO5SSi | 详情 | 详情 | |
| (III) | 26401 | 8-(Benzyloxymethoxy)-2-[6-bromo-4-O-(2-chloroacetyl)-2,6-dideoxy-2-(phenylsulfanyl)-3-O-(triethylsilyl)-beta-D-glucopyranosyloxy]-6,9-bis(2(E)-butenyloxy)-3(S)-[1(S)-methoxy-2-[5(R)-methylspiro[1,3-dioxolane-2,1'-cyclopent]-4(S)-yl]-2-oxoethyl]-1,2,3,4-tetrahydroanthracen-1-one; 8-(Benzyloxymethoxy)-2-[6-bromo-4-O-(2-chloroacetyl)-2,6-dideoxy-2-(phenylsulfanyl)-3-O-(triethylsilyl)-beta-D-glucopyranosyloxy]-6,9-bis(2(E)-butenyloxy)-3(S)-[1(S)-methoxy-2-[5(R)-methylspiro[1,3-dioxolane-2,1'-cyclopent]-4(S)-yl]-2-oxoethyl]-1,2,3,4-tetrahydroanthracen-1-one | C61H76BrClO14SSi | 详情 | 详情 | |
| (IV) | 26402 | 8-(Benzyloxymethoxy)-2-[6-bromo-4-O-(2-chloroacetyl)-2,6-dideoxy-2-(phenylsulfanyl)-3-O-(triethylsilyl)-beta-D-glucopyranosyloxy]-6-(2-chloroacetoxy)-9-hydroxy-3(S)-[1(S)-methoxy-2-[5(R)-methylspiro[1,3-dioxolane-2,1'-cyclopent]-4(S)-yl]-2-oxoethyl]-1,2,3,4-tetrahydroanthracen-1-one; 8-(Benzyloxymethoxy)-2-[6-bromo-4-O-(2-chloroacetyl)-2,6-dideoxy-2-(phenylsulfanyl)-3-O-(triethylsilyl)-beta-D-glucopyranosyloxy]-6-(2-chloroacetoxy)-9-hydroxy-3(S)-[1(S)-methoxy-2-[5(R)-methylspiro[1,3-dioxolane-2,1'-cyclopent]-4(S)-yl]-2-oxoethyl]-1,2,3,4-tetrahydroanthracen-1-one | C49H51BrCl2O15S | 详情 | 详情 | |
| (V) | 26403 | (2S,3S,4R,5R,6S)-6-([(2S,3S,4S,5R,6R)-2-(bromomethyl)-3-[(2-chloroacetyl)oxy]-5-(phenylsulfanyl)-6-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4-hydroxy-5-iodo-2,4-dimethyltetrahydro-2H-pyran-3-yl 2-methylpropanoate | C27H33BrCl4INO9S | 详情 | 详情 | |
| (VI) | 26404 | C72H81Br2Cl2IO22S2 | 详情 | 详情 | ||
| (VII) | 26405 | (2R,3S,4S,5R,6S)-6-hydroxy-4-[[(2R,3S,4S,5R,6R)-4-hydroxy-3-iodo-5-methoxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-2-methyl-5-(phenylselanyl)tetrahydro-2H-pyran-3-yl acetate | C21H29IO8Se | 详情 | 详情 | |
| (VIII) | 26406 | C93H108Br2Cl2I2O29S2Se | 详情 | 详情 |
合成路线2
The elimination of the diol protecting group of compound (VIII) with CSA in methanol followed by silylation with TES triflate affords the silylated pentasaccharide (IX), which is finally desulfurized and deiodinated by hydrogenolysis with Et3B and Bu3SnH, and with RaNi to eliminate also the BOM protecting group, and with FH in pyridine to eliminate the silyl and chloroacetyl groups affording the target olivomycin A.
