合成路线:In a further synthetic procedure,ketalization of enone (CV) with ethyleneglycol afforded (CVI).After silylation of the primary alcohol group of (CVI) to (CVII),allylic oxidation by means of tert-butyl hydroperoxide and Cr(CO)6 furnished ketone (CVIII).Catalytic hydrogenation of the double bond of (CVIII) to (CIX),followed by ketone reduction with K-Selectride,gave the C-7 alcohol (CX),which was esterified with benzoyl chloride,yielding benzoate ester (CXI).Subsequent desilylation of (CXI) using tetrabutylammonium fluoride provided (CXII).
合成路线:Alcohol (CXII) was converted to aldehyde (CXIII) either by Swern oxidation or by means of NaOCl and TEMPO.The Horner-Emmons condensation of phosphonate (CXV) (prepared from bromo ketone (CXIV) and triethyl phosphite) with aldehyde (CXIII) furnished the unsaturated ketone (CXVI).Asymmetric reduction of the carbonyl group of (CXVI) was accomplished by means of borane-dimethyl sulfide complex in the presence of (S)-MeCBS,yielding (CXVII).Catalytic hydrogenation of the resultant allylic alcohol (CXVII) afforded (CXVIII).The ethylene ketal group of (CXVIII) was then hydrolyzed under acidic conditions to the ketone (CXIX).
合成路线:Treatment of the OH group of (CXIX) with SO3-pyridine provided sulfate (CXX).The benzoate ester of (CXX) was subsequently hydrolyzed under basic conditions to give (CXXI).Reductive amination of (CXXI) with the cyanodiamine (CXXII) afforded (CXXIII).The cyano group of (CXXIII) was finally reduced to the target amine by catalytic hydrogenation.
参考文献标题:Stereoselective synthesis of 24-hydroxylated cpds.useful for the preparation of aminosterols,vitamin D analogs,and other cpds.
文献作者:Kinney,W.A.; Meckler,H.; Zhang,X.; Lee,N.; Jones,S.; Rao,M.N.; Bulliard,M.(Genaera Corp.)
参考来源:WO 9824800
合成路线:Steroid (CV) was treated with the fungal species Diplodia gossipina to yield the 7-hydroxylated compound (CXXXII) as a fermentation metabolite.Reduction of enone (CXXXII) by lithium in liquid ammonia afforded the saturated ketone (CXXXIII),which was subsequently protected as the ethylene ketal (CXXXIV) by treatment with ethylene glycol and chlorotrimethylsilane.Selective oxidation of the C-22 alcohol group of (CXXXIV) with NaOCl in the presence of TEMPO provided aldehyde (CXXXV).Wadsworth-Emmons condensation of (CXXXV) with phosphonate (CXV) gave enone (CXXXVI).Stereoselective reduction of (CXXXVI) to the 24-(S)-alcohol (CXXXVII) was achieved by treatment with borane-tetrahydrofuran complex in the presence of the chiral catalyst (R)-MeCBS.After catalytic hydrogenation of the double bond of (CXXXVII),the resultant ketal (CXXXVIII) was hydrolyzed to ketone (CXXXIX) under acidic conditions.Sulfation of (CXXXIX) by means of sulfur trioxide-pyridine furnished the key precursor (CXXI),which was then reductively aminated as in the precedent Scheme
参考文献标题:A process for the preparation of 7alpha-hydroxy 3-aminosubstd.sterols using intermediates with an unprotected 7alpha-hydroxy group
文献作者:Kinney,W.A.; Zhang,X.; Michalak,R.(Genaera Corp.)
参考来源:WO 0179255
合成路线:Steroid (CV) was treated with the fungal species Diplodia gossipina to yield the 7-hydroxylated compound (CXXXII) as a fermentation metabolite.Reduction of enone (CXXXII) by lithium in liquid ammonia afforded the saturated ketone (CXXXIII),which was subsequently protected as the ethylene ketal (CXXXIV) by treatment with ethylene glycol and chlorotrimethylsilane.Selective oxidation of the C-22 alcohol group of (CXXXIV) with NaOCl in the presence of TEMPO provided aldehyde (CXXXV).Wadsworth-Emmons condensation of (CXXXV) with phosphonate (CXV) gave enone (CXXXVI).Stereoselective reduction of (CXXXVI) to the 24-(S)-alcohol (CXXXVII) was achieved by treatment with borane-tetrahydrofuran complex in the presence of the chiral catalyst (R)-MeCBS.After catalytic hydrogenation of the double bond of (CXXXVII),the resultant ketal (CXXXVIII) was hydrolyzed to ketone (CXXXIX) under acidic conditions.Sulfation of (CXXXIX) by means of sulfur trioxide-pyridine furnished the key precursor (CXXI),which was then reductively aminated as in the precedent Scheme
参考文献标题:A short formal synthesis of squalamine from a microbial metabolite
文献作者:Kinney,W.A.; Zhang,X.; Williams,J.I.; Johnston,S.; Michalak,R.S.; Deshpande,M.N.; Dostal,L.; Rosazza,J.P.
参考来源:Org Lett 2000,2(19),2921
合成路线:Intermediate (CXXXIX) has been prepared by a new synthetic procedure:The known methyl 3-keto-5-alpha-chenodeoxycholanate (CXL) was protected as the methoxymethyl ether (CXLI) by treatment with dimethoxymethane and P2O5.Further protection of the keto group of (CXLI) as the ethylene ketal (CXLII),followed by reduction with LiAlH4,afforded alcohol (CXLIII).Swern oxidation of alcohol (CXLIII) yielded aldehyde (CXLIV).This was subjected to Wittig condensation with isopropylidene triphenylphosphorane to give olefin (CXLV).Sharpless asymmetric dihydroxylation of olefin (CXLV) furnished the target diol (CXLVI).Selective esterification of the secondary alcohol of (CXLVI) with Ac2O in pyridine gave rise to acetate (CXLVII).
合成路线:The tertiary alcohol group of (CXLVII) was dehydrated to (CXLVIII) upon treatment with methanesulfonyl chloride and triethylamine.Diimide reduction of the olefin double bond of (CXLVIII) produced (CXLIX).The acetate ester of (CXLIX) was further hydrolyzed to alcohol (CL) by methanolic KOH.Then,acidic hydrolysis of the ketal protecting groups of (CL) furnished the key precursor (CXXXIX).
参考文献标题:A new highly stereoselective construction of the sidechain of squalamine through improved Sharpless catalytic asymmetric dihydroxylation
文献作者:Zhou,X.D.; et al.
参考来源:Tetrahedron Lett 2001,42(13),2537
合成路线:In a further synthetic strategy,an azido precursor of spermidine (CXXX) was used in the reductive amination step.Condensation between 1,3-diaminopropane (CXXIV) and 4-chloro-1-butanol (CXXV) provided the diamino alcohol (CXXVI).Protection of the amino groups of (CXXVI) with di-tert-butyl dicarbonate yielded alcohol (CXXVII),which was converted to mesylate (CXXVIII) by treatment with methanesulfonyl chloride and triethylamine.Subsequent mesylate displacement in (CXXVIII) with NaN3 in DMF furnished the di-Boc-protected azide (CXXIX).The Boc protecting groups of (CXXIX) were then removed by treatment with HCl to give the desired diamino azide (CXXX).Reductive amination of the 3-keto steroid (CXXI) with amine (CXXX) yielded the 3-beta amino steroid (CXXXI).The azido group of (CXXXI) was finally reduced to the title triamino compound by catalytic hydrogenation over Raney-Ni.
参考文献标题:Synthesis of an azido spermidine equivalent
文献作者:Weis,A.L.; et al.
参考来源:Tetrahedron Lett 1999,40(26),4863
合成路线:Removal of the Boc and silyl protecting groups of (XLI) was accomplished by treatment with trifluoroacetic acid in chloroform to provide,after chromatographic separation,the 3-alpha-polyamino sterol (XLII).Subsequent catalytic hydrogenation removed the benzyl protecting group of (XLVII),yielding (XLIII).Finally,sulfation of alcohol (XLIII) with sulfur trioxide-pyridine gave rise to the title compound.
合成路线:Alcohol (CXII) was converted to aldehyde (CXIII) either by Swern oxidation or by means of NaOCl and TEMPO.The Horner-Emmons condensation of phosphonate (CXV) (prepared from bromo ketone (CXIV) and triethyl phosphite) with aldehyde (CXIII) furnished the unsaturated ketone (CXVI).Asymmetric reduction of the carbonyl group of (CXVI) was accomplished by means of borane-dimethyl sulfide complex in the presence of (S)-MeCBS,yielding (CXVII).Catalytic hydrogenation of the resultant allylic alcohol (CXVII) afforded (CXVIII).The ethylene ketal group of (CXVIII) was then hydrolyzed under acidic conditions to the ketone (CXIX).
合成路线:Treatment of the OH group of (CXIX) with SO3-pyridine provided sulfate (CXX).The benzoate ester of (CXX) was subsequently hydrolyzed under basic conditions to give (CXXI).Reductive amination of (CXXI) with the cyanodiamine (CXXII) afforded (CXXIII).The cyano group of (CXXIII) was finally reduced to the target amine by catalytic hydrogenation.
参考文献标题:Synthesis of squalamine utilizing a readily accessible spermidine equivalent
文献作者:Zhang,X.; et al.
参考来源:J Org Chem 1998,63(23),8599
产品链接: CAS No. 148717-90-2›› 产品链接: CAS No.320725-47-1››