合成路线:Alternatively,intermediate omuralide (XI) can also be obtained by following this synthetic sequence: Methylsulfanyl derivative (LVII) is transformed into chiral mono ester (LVIII) by enantioselective hydrolysis with porcine liver esterase (PLE) followed by recrystallization of the quinine salt.Treatment of (LVIII) with oxalyl chloride in DMF,followed by coupling in dichloromethane with N-p-methoxybenzylglycinate (PMB-NHCH2COOMe) (B) and Et3N and subsequent Dieckmann cyclization with LDA in THF,affords keto lactam (LIX).Stereoselective alpha-hydroxymethylation of (LIX) by means of formalin and DBU in THF,followed by stereospecific reduction with NaBH(OAc)3 in AcOH,gives dihydroxy lactam (LX),which is then converted into TBDMS ether (LXI) by the following sequence: i) esterification of primary hydroxyl group by pivaloyl chloride (PivCl) in pyridine; ii) silylation of the secondary hydroxyl group by means of TBSOTf and 2,6-lutidine; and iii) cleavage of the pivalate ester by treatment with NaOMe in MeOH.Desulfurization of (LXI) with Ni Raney followed by Dess-Martin periodinane oxidation furnishes aldehyde (LXII),which then reacts with Grignard reagent (LXIII) and TMSCl to yield the addition product (LXIV).Hydrogenation of (LXIV) over Pd/C followed by desilylation with TFA/H2O produces (LXV),which is hydrolyzed by means of LiOH in THF/H2O and treated with BOP-Cl and Et3N,affording beta-lactone (LXVI).Finally,cleavage of the N-p-methoxybenzyl protecting group of (LXVI) with Ceric ammonium nitrate in acetonitrile/H2O yields omuralide (XI).
参考文献标题:An efficient and concise enantioselective total synthesis of lactacystin
文献作者:Corey,E.J.; et al.
参考来源:Angew Chem.Int Ed Engl 1998,37(12),1676
合成路线:Sharpless epoxidation of (XIII) with cumene hydroperoxide,diisopropyl L-tartrate ((+)-DIPT) and Ti(O-i-Pr)4 affords epoxide (-)-(XIV),which is then treated with benzyl isocyanate and NaH in refluxing THF to yield oxazolidinone (XV).Oxidation of (XV) by means of CrO3 in H2SO4 (Jones reagent) in acetone gives the corresponding carboxylic acid (XVI),which is converted into methyl ester (XVII) via diazomethane esterification in Et2O.Exposure of (XVII) to ethanolic KOH affords the trans-acid (XVIII),which is then converted into (2R,3S)-hydroxyleucine (XIX) by treatment with KOH and hydrogenolysis over Pd(OH)2 in MeOH.Esterification of (XIX) by means of MeOH and HCl (gas) provides (XX),which is treated with methyl benzimidate (Ph(MeO)C=NH) or methyl orthobenzoate (PhC(OMe)3) in the presence of catalytic p-TsOH to yield trans-oxazoline (XXI).Aldol condensation of (XXI) with formaldehyde and LHMDS via the Seebach protocol gives (XXII),which is converted into (XXIII) via Moffat oxidation with DCC and TFA in benzene/DMSO.Brown asymmetric allylboration of (XIII) in THF with (E)-crotyl(diisopinocampheyl)borane (XXIV) in Et2O affords a homoallylic alcohol mixture from which diastereomer (-)-(XXV) is obtained.Ozonolysis of (-)-(XXV) and reductive treatment with dimethylsulfide (DMS),followed by oxidation with NaClO2,NaH2PO4 and 2-methyl-2-butene,provides carboxylic acid (XXVI),which is then converted into (X) by means of Pd and HCOONH4 in refluxing HOAc followed by saponification with NaOH.Lactam ester derivative (X) reacts with N-acetyl-L-cysteine allyl ester (XXVII),BOPCl and Et3N in CH2Cl2 to furnish (XVIII),which is finally deallylated by means of Pd(PPh3)4,HCO2H and Et3N in THF.
参考文献标题:Total synthesis of (+)-lactacystin,the first non-protein neurotrophic factor
文献作者:Sunazuka,T.; et al.
参考来源:J Am Chem Soc 1993,1155302
合成路线:Methylation of bicyclic oxazolidine (XXIX) by means of LDA and MeI,followed by selenenylation with PhSeBr/LDA in THF and ozonolysis in CH2Cl2,affords unsaturated derivative (XXX).Treatment of (XXX) with Tbdms-OTf and 2,6-lutidine in CH2Cl2 yields silyloxypyrrole (XXXI),which is converted into (XXXII) by an aldol reaction with (II) in the presence of SnCl4 in Et2O.Acetylation of (XXXII) by means of Ac2O,pyridine followed by dihydroxylation with OsO4 and N-methylmorpholine N-oxide allows formation of diol (XXXIII),whose tertiary hydroxyl group is removed by means of N,N'-thiocarbonyldiimidazole,followed by reduction with Bu3SnH and catalytic AIBN in toluene to provide derivative (XXXIV).Treatment of (XXXIV) with NaOH in MeOH followed by hydrogenolysis over Pd/C in HCl yields derivative (XXXV),which is converted into (XXXVI) by protection of primary alcohol by means of Et3SiCl and acetylation of secondary alcohol by treatment with Ac2O in pyridine.Regeneration of primary alcohol by treatment of (XXXVI) with HF in CH3CN furnishes (XXXVII),which is then oxidized by means of Jones reagent to yield (XXXVIII).Finally,saponification of diacetate acid (XXXVIII) with NaOH gives lactam (X).
参考文献标题:Stereocontrolled Mukaiyama-type aldol reaction of siloxypyrroles derived from (S)-glutamic acid
文献作者:Uno,H.; et al.
参考来源:Synlett 1997,390
合成路线:Methylation of bicyclic oxazolidine (XXIX) by means of LDA and MeI,followed by selenenylation with PhSeBr/LDA in THF and ozonolysis in CH2Cl2,affords unsaturated derivative (XXX).Treatment of (XXX) with Tbdms-OTf and 2,6-lutidine in CH2Cl2 yields silyloxypyrrole (XXXI),which is converted into (XXXII) by an aldol reaction with (II) in the presence of SnCl4 in Et2O.Acetylation of (XXXII) by means of Ac2O,pyridine followed by dihydroxylation with OsO4 and N-methylmorpholine N-oxide allows formation of diol (XXXIII),whose tertiary hydroxyl group is removed by means of N,N'-thiocarbonyldiimidazole,followed by reduction with Bu3SnH and catalytic AIBN in toluene to provide derivative (XXXIV).Treatment of (XXXIV) with NaOH in MeOH followed by hydrogenolysis over Pd/C in HCl yields derivative (XXXV),which is converted into (XXXVI) by protection of primary alcohol by means of Et3SiCl and acetylation of secondary alcohol by treatment with Ac2O in pyridine.Regeneration of primary alcohol by treatment of (XXXVI) with HF in CH3CN furnishes (XXXVII),which is then oxidized by means of Jones reagent to yield (XXXVIII).Finally,saponification of diacetate acid (XXXVIII) with NaOH gives lactam (X).
参考文献标题:Total synthesis of (+)-lactacystin from (R)-glutamate
文献作者:Uno,H.; et al.
参考来源:J Am Chem Soc 1994,116(5),2139
合成路线:Sharpless epoxidation of (XIII) with cumene hydroperoxide,diisopropyl L-tartrate ((+)-DIPT) and Ti(O-i-Pr)4 affords epoxide (-)-(XIV),which is then treated with benzyl isocyanate and NaH in refluxing THF to yield oxazolidinone (XV).Oxidation of (XV) by means of CrO3 in H2SO4 (Jones reagent) in acetone gives the corresponding carboxylic acid (XVI),which is converted into methyl ester (XVII) via diazomethane esterification in Et2O.Exposure of (XVII) to ethanolic KOH affords the trans-acid (XVIII),which is then converted into (2R,3S)-hydroxyleucine (XIX) by treatment with KOH and hydrogenolysis over Pd(OH)2 in MeOH.Esterification of (XIX) by means of MeOH and HCl (gas) provides (XX),which is treated with methyl benzimidate (Ph(MeO)C=NH) or methyl orthobenzoate (PhC(OMe)3) in the presence of catalytic p-TsOH to yield trans-oxazoline (XXI).Aldol condensation of (XXI) with formaldehyde and LHMDS via the Seebach protocol gives (XXII),which is converted into (XXIII) via Moffat oxidation with DCC and TFA in benzene/DMSO.Brown asymmetric allylboration of (XIII) in THF with (E)-crotyl(diisopinocampheyl)borane (XXIV) in Et2O affords a homoallylic alcohol mixture from which diastereomer (-)-(XXV) is obtained.Ozonolysis of (-)-(XXV) and reductive treatment with dimethylsulfide (DMS),followed by oxidation with NaClO2,NaH2PO4 and 2-methyl-2-butene,provides carboxylic acid (XXVI),which is then converted into (X) by means of Pd and HCOONH4 in refluxing HOAc followed by saponification with NaOH.Lactam ester derivative (X) reacts with N-acetyl-L-cysteine allyl ester (XXVII),BOPCl and Et3N in CH2Cl2 to furnish (XVIII),which is finally deallylated by means of Pd(PPh3)4,HCO2H and Et3N in THF.
参考文献标题:Total synthesis of (+)-lactacystin
文献作者:Nagamitsu,T.; et al.
参考来源:J Am Chem Soc 1996,118(15),3584
合成路线:Treatment of allofuranose derivative (XXXIX) with Bu2SnO in toluene followed by treatment with benzyl bromide and CsF provides (XL),which is then oxidized with Jones reagent to afford ketone (XLI).Wittig reaction of (XLI) with (ethoxycarbonymethylene)triphenylphosphorane (XLII) in toluene yields olefin (XLIII),which is then reduced by means of DIBAL to give (XLIV).Alcohol (XLIV) is then converted into trichloroacetimidate (XLV) by treatment with NaH and trichloroacetonitrile (CCl3CN) in Et2O.Rearrangement of (XLV) by heating with toluene affords derivative (XLVI),which is hydrolyzed by means of TFA/H2O to yield a mixture of diols that are chromatographically separated,providing (XLVII).Oxidation of (XLVII) in MeOH by means of NaIO4 provides hemiaminal derivative (XLVIII),which is further oxidized with Jones reagent to afford lactam (IL).Removal of protecting (N-trichloroacetyl and O-formyl) groups by treatment of (IL) with NaBH4 in MeOH gives partially deprotected derivative (L).
合成路线:Silylation of (L) by treatment with TBSOTf and 2,6-lutidine in CH2Cl2 furnishes (LI),whose benzyl group is removed by means of Na/NH3 in THF to yield (LII).Moffat oxidation of (LII) gives aldehyde (LIII),which is treated with isopropylmagnesium bromide (LIV) in THF to afford a mixture of adducts from which (LV) is chromatographically separated.Treatment of (LV) with TFA/H2O provides (LVI),which is then treated with O3 (DMS workup) and finally oxidized with HOSO2NH2,NaH2PO4 and NaClO2 to yield carboxylic acid (X).
参考文献标题:Stereoselective total synthesis of (+)-lactacystin from D-glucose
文献作者:Chida,N.; et al.
参考来源:Tetrahedron 1997,53(48),16287
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