Synthesis of Protected Dithiol Amino Acids for Potential Use in Peptide Chemistry

Two N-Fmoc and S,S′-protected α-amino acids were synthesized by introducing the derivatives of dithioether into a Tyrosine side chain under the Mitsunobu protocol using the diisopropylazodicarboxylate/triphenylphosphine (DIAD/TPP) system. These amino acids provide a potential use in peptide chemistry.     

An Efficient Procedure for Cleavage of T-Butyl Protected Cysteine in Solid Phase Peptide Synthesis

In the Fmoc-strategy of solid phase peptide synthesis, 1M trimethylsilyl bromide-thioanisole/trifluoroacetic acid in the presence of 1,2-ethanedithiol as scavenger was found to be an efficient deprotecting procedure for a full cleavage and side chains deprotection of the peptide resin involving t-butyl protected cysteine. In addition, selective deprotection of the peptide resin containing protected cysteine was also described based on this method.     

5-Spirocyclopropane Isoxazolidines as Versatile Intermediates in Organic Synthesis

Summary. The review outlines the various different azaheterocycles available from 5-spirocyclopropane isoxazolidines. These compounds can be regarded as versatile direct precursors of tetrahydro-, dihydropyridone and azetidinone derivatives. The current scope and limitations, and the selectivity aspects of the different processes are discussed therein.     

5-Spirocyclopropane Isoxazolidines as Versatile Intermediates in Organic Synthesis

The review outlines the various different azaheterocycles available from 5-spirocyclopropane isoxazolidines. These compounds can be regarded as versatile direct precursors of tetrahydro-, dihydropyridone and azetidinone derivatives. The current scope and limitations, and the selectivity aspects of the different processes are discussed therein.     

Synthesis and Evaluation of Enantiomeric Purity of Protected α-Amino and Peptide Aldehydes

The synthesis of enantiomerically pure Ac-Tyr-Val-Ala-Asp(O^tBu)-H dimethyl acetal ((S)- 1 ) is reported, a protected tetrapeptide C-terminal aldehyde belonging to a class of potent, reversible inhibitors of cysteine proteases (e.g., interleukin-1β-converting enzyme (ICE), also called caspase-1). The coupling of the precursors Ac-Tyr-Val-Ala-OH ((S)- 8 ) and H-Asp(O^tBu)-H dimethyl acetal ((S)- 6 ) gave (S)- 1 in a yield of 85%, with epimerization of <2% at the alanine and aspartic-acid residue. (S)- 6 itself was synthesized in four steps in an overall yield of 83% with an ee >98%.     

柠檬醛及中间体的合成

以异戊烯醛和异戊烯醇为原料,经异戊烯酸催化缩醛化反应得到3-甲基-2-丁烯醛二异戊烯基缩醛,再经磷酸二氢铵催化消除反应得到顺/反-异戊二烯基-3-甲基丁二烯醚,并进一步热重排获得柠檬醛。研究了缩醛化反应条件和消除反应条件对转化率的影响。结果表明,以0.3%异戊烯酸为酸性催化剂,70～75℃共沸脱水反应8 h,异戊烯醛的单程转化率达到63%～64%,处理后可得含量为97.5%的3-甲基-2-丁烯醛二异戊烯基缩醛,收率96.8%;以0.2%～0.5%磷酸二氢铵为催化剂,100～130℃,2.66 kPa下反应并及时将反应产物蒸出,处理后得到含量为95.9%的顺/反-异戊二烯基-3-甲基丁二烯醚,收率97.0%。顺/反-异戊二烯基-3-甲基丁二烯醚在120～130℃重排反应1 h,其反应产物柠檬醛含量97.5%,收率90.2%。     

两种氮杂环丁烷类药物中间体的合成

1-二苯甲基-3-羟基氮杂环丁烷(1)经过对甲苯磺酰氯取代、叠氮化及还原反应合成了药物中间体--1-二苯甲基-3-氨基氮杂环丁烷(4);1经过氧化、氰基化与还原反应合成了1-二苯甲基-3-羟基-3-氨甲基氮杂环丁烷(8).4和8的结构经1H NMR表征.     

稀有酮糖中间体的合成

以全苄基保护的糖酸内酯为原料,通过正丁基锂/二碘甲烷生成的碘甲基锂试剂对底物羰基加成增长碳链,再在碱性环境中水解合成了5个稀有酮糖中间体,其结构经NMR确认。     

多肽片段连接方法及肽硫酯和肽醛的合成*

本文综述了多肽和蛋白质合成中的片段连接方法,这是近年来多肽和蛋白质合成领域中方法学上的重要进展.该方法使用非保护的多肽片段,无需酶或化学活化试剂,在缓冲溶液中能够高产率地获得多肽和蛋白质.还介绍了与多肽片段连接有关的肽硫酯和肽醛的合成方法.     

Stereoselective Synthesis of Versatile Intermediates for Clerodanes Total synthesis

The stereoselective synthesis of compounds 2a-d, attractive intermediates for the synthesis of clerodane diterpenes is described in 6 to 9 steps in good overall yields from commercially available racemic Wieland-Miescher ketone.     

Synthesis of Intermediates by Rhodium-Catalyzed Hydroformylation

The reaction of olefins with carbon monoxide and hydrogen to give aldehydes is referred to as hydroformylation (oxo reaction). As catalyst for this reaction rhodium is about three to four orders of magnitude more active than the more commonly employed cobalt. With special rhodium compounds, e.g. di-ν-chlorobis(ν-1,5-cyclooctadiene)dirhodium [RhCl(C₈H₁₂)]₂, in the presence of chiral phosphanes, even asymmetric hydroformylations can be achieved; however, the enantiomeric purity of the products (20–30%) is not high enough for industrial-scale syntheses.     

N-tert-Butyldimethylsilyl Imines as Intermediates for the Synthesis of Amines and Ketones

Grignard reagents add to benzonitrile at low temperature catalyzed by CuBr and TBSCl affording N-TBS ketimines, which were investigated as intermediaries for the synthesis of primary amines and ketones. N-silylimines were easily obtained by an organolithium addition to benzonitrile followed by a reaction with TBSCl in CH₂Cl₂. In situ reduction of these imines by BH₃ and 1,3,2-oxazaborolidines 1 or 2 as chiral templates afforded the corresponding amines with modest to good enantiomeric excess.     

An Alternative Stereoselective Synthesis of Protected Trans-5-Alkyl-4-Hydroxy-2-Pyrrolidinones

A flexible approach to protected trans-5-alkyl-4-hydroxy-2-pyrrolidinones was described. The key step involved the α-amidoalkylation of benzene-sulfone derived from (S)-malic acid, with organozinc reagents generated in situ from Grignard reagents and anhydrous ZnCl₂-OEt₂.     

全保护RGD三肽的合成方法研究

以两条路线、多种偶联试剂(DCC，EDCI，CDI，EEDQ)合成了全保护三肽Arg- Gly-Asp(RGD)．Boc-Arg(Tos)-OH经上述偶联剂短时活化，于合适条件下与Ts0H- G1y-OBzl缩合，均获得良好收率(43％-97％)．经Pd(OH)2／H2还原得到的Boc-Arg (Tos)-G1y-0H于22-27℃与HCl·Asp(OcHex)-OBzl偶联得到全保护三肽Boc-Arg (Tos)-Gly-Asp(OcHex)-OBzl(TM)，反应收率分别为76．4％(DCC／HOSu)，64．7％ -78．3％(DCC／HOBt)，66．7％-77．9％(EDCI／HOBt)．Boc-Gly-OH和HCl·Asp- (OcHex)-OBzl经DCC／HOBt或CDI活化，可得到碳端二肽Boc-Gly-Asp(OcHex)-OBzl (收率分别为81．2％，89．5％)，该二肽脱Boc后与Boc-Asp(Tos)-OH反应，经DCC ／HOBt，EDCI／HOBt，CDI，DCC／HOSu活化，均可生成目标分子TM，其反应收率分 别为40．4％，73．8％，67．8％，84．4％．     

正交保护赖氨酸的合成

具有不同氨基保护基的赖氨酸在树状,环状多肽及糖肽等的合成中非常重要,以Ｄｄｅ、Ｆｍｏｃ,Ａｌｏｃ和Ｚ为保护基合成了６种正交保护的赖氨酸。