合成路线:In a different synthetic strategy,the known Garner's aldehyde (I) is subjected to a Wittig reaction with phosphorane (II) to give the unsaturated ester (III),which is subsequently hydrogenated,producing (IV) as an inseparable mixture of diastereoisomers.Oxazolidine hydrolysis in (IV),followed by cyclization under acidic conditions leads to lactone (V).This is then converted to the thiolactone (VI) upon treatment with Lawesson's reagent in hot toluene.Condensation of thiolactone (VI) with the Wittig reagent (VII),followed by double bond isomerization in the presence of DBU furnishes the dihydropyran derivative (VIII).Stereoselective hydrogenation of the double bond of (VIII) with PtO2 gives rise to the desired all-cis isomer (IX).The methyl vester group of (IX) is then reduced to aldehyde (X) by means of DIBAL in cold toluene.
合成路线:Wittig reaction of aldehyde (X) with phosphorane (II) produces the unsaturated ester (XI),which is further reduced to the allylic alcohol (XII) with DIBAL in toluene.Treatment of (XII) with CBr4 and PPh3 leads to allyl bromide (XIII).This is then condensed with sodium p-toluenesulfinate (XIV),providing sulfone (XV).Subsequent acidic Boc group cleavage gives amine (XVI).
合成路线:Horner-Emmons condensation of aldehyde (XVII) with phosphonate (XVIII) gives rise to the Z-olefin (XIX).After ester group hydrolysis,the resultant carboxylic acid (XX) is coupled to amine (XVI) by using HBTU to produce amide (XXI).
合成路线:2-Deoxy-D-glucose (XXII) is protected as the cyclic acetal (XXIV) employing p methoxybenzaldehyde dimethyl acetal (XXIII) in the presence of TsOH.Subsequent oxidation of the anomeric hydroxyl group of (XXIV) with Br2 leads to lactone (XXV).After protection of the remaining 3-hydroxyl group of (XXV) as the silyl ether (XXVI),olefination with the Tebbe reagent provides the exocyclic vinyl ether (XXVII).Treatment of (XXVII) with PPTS and MeOH affords a separable mixture of epimeric methylketals (XXVIII).Desilylation of the desired isomer yields alcohol (XXIX),which is then oxidized to ketone (XXX) employing the Dess-Martin periodinane reagent.
合成路线:Tebbe methylenation of ketone (XXX) gives the exo-olefin (XXXI).The p methoxybenzylidene acetal moiety of (XXXI) is then reduced with DIBAL to generate the p-methoxybenzyl ether (XXXII).The free hydroxyl group of (XXXII) is then acylated with pivaloyl chloride,providing pivalate ester (XXXIII).Removal of the p-methoxybenzyl group of (XXXIII) by treatment with DDQ,followed by reprotection of the resultant alcohol (XXXIV) with t-butyldimethylsilyl triflate leads to silyl ether (XXXV).The pivalate ester group of (XXXV) is then cleaved by treatment with DIBAL to afford alcohol (XXXVI),which is oxidized to aldehyde (XXXVII) by using the Dess-Martin periodinane.
合成路线:Condensation of sulfone (XXI) with aldehyde (XXXVII),followed by treatment with benzoyl chloride affords adduct (XXXVIII).Reductive elimination of sulfone (XXXVIIII) with sodium amalgam leads to the conjugated diene (XXXIX).Both O-silyl groups of (XXXIX) are removed by treatment with tetrabutylammonium fluoride,providing diol (XL).Then,esterification of (XL) with acetic anhydride and DMAP furnishes diacetate (XLI).
合成路线:Treatment of diester (XLI) with LiOH produces a mixture of hydrolyzed products,from which the desired mono-acetylated compound (XLII) can be separated from its mono-acetyl regiosiomer and the fully hydrolyzed product.Epoxidation of the exocyclic olefin (XLII) with m-CPBA furnishes diastereoselectively epoxide (XLIII).Finally,deacetylation of the methyl ketal (XLIII) to the target hemiketal compound is achieved by treatment with an acidic cation-exchange resin in wet THF.
参考文献标题:A synthesis of FR901464
文献作者:Horigome,M.; Motoyoshi,H.; Watanabe,H.; Kitahara,T.
参考来源:Tetrahedron Lett 2001,42(46),8207
产品链接: CAS No. 146478-72-0››