d-生物素的不对称全合成研究(Ⅱ)

1,3－二苄基咪唑啉－2－酮－顺－4,5－二羟酸经脱水、单酯化,折分成分（4S,5R）－顺1,3－二苄基－5－甲氧基羧基－2－氧代咪唑啉－4－羧酸,再经还原环合,硫代成(3aS,6aR)-1,3－二苄基－四氢－4H－噻吩并[3,4-d)咪唑－2,4（1H)-二酮（7）,后者经格氏反应、脱水、还原、裂解环合一锅合成（3aR,8aS,8bS)－1,3－二苄基－2－氧代十氢咪唑[3,4-d]噻吩并[1,2-a]锍翁溴化物（11）,继而经缩合、开环、水解、脱羧、脱苄而得d－生物素（1）,总收率为14．5％。     

利用手性N-氰乙基-2-羟基蒎烷-3-酮亚胺合成光学活性2-乙基环丙烷氨基酸

以２－羟基蒎烷－３－酮（１）与氨基乙腈缩合得到的手性酮亚胺（２）为中间体，经去质子化，在Ｐｄ（０）催化下与１，４－二氯－２－丁烯（３）发生串联反应，得到光学活性环丙烷衍生物（４），产率约为７０％，反应的非对映立体选择性（ｄ．ｅ．）为１００％．化合物４经选择性还原后水解，即可制得光学活性２－乙基环丙烷氨基酸，产物的对映体过量（ｅ．ｅ．）为３３％．     

1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二羧酸二(2-甲氧基乙基)酯的合成

对1，4－二氢吡啶类钙拮抗剂西尼地平进行了结构修饰。以双乙烯酮和乙二醇单甲醚为原料，经酯化、缩合、氨化和Hantzsch环化等反应合成了1，4－二氢－2，6二甲基－4－（3－硝基苯基）－3，5－吡啶二羟酸二（2－甲氧基乙基）酯，总收率71％。目标产物结构经^1H NMR和MS确证。     

2,3-二氢-3,5-二羟基-6-甲基-4(H)吡喃-4-酮的合成及热裂解行为

以葡萄糖和哌啶为原料，合成、分离并鉴定了2，3－二氢－3，5－二羟基－6－甲基－4－（H）吡喃－4－酮（1），以空气氛下直接热裂解，SPME吸附热裂解挥发生产物的方式，分析鉴定了20个裂解的挥发性化合物，讨论了热裂解的可能过程。     

2-(1H-唑基)-1-(2,3,4-三甲氧基)苯乙酮衍生物的合成与结构表征

首先以2－溴－1－（2，3，4－三甲氧基）苯乙酮，四丁基铵－1H－1，2，4－三唑或咪唑为原料，分别合成了2－（1H－1，2，4－三唑－1－基）－1－（2，3，4－三甲氧基）苯乙酮（Ia)和2－（1H－咪唑0－1－基）－1－（2，3，4－三甲氧基）苯乙酮（Ib)与盐酸羟胺反应生成2－（1H－1，2，4－三唑－1－基）－1－（2，3，4－三甲氧基）苯乙酮肟和1－（1H－咪唑－1－基）－1－（2，3，4三甲氧基）苯乙酮肟，产率为63％－72％，并经元素分析，IR和1H NMR进行了表征。     

(1S,6R)-1-羟基-6-(1,3-苯并二硫-2-氧)-3,5-环维生素D2的合成

以VD2为原料制备了1α，25－二羟基维生素D3的重要中间体（1S，6R）－1－羟基－6－（1，3－苯并二硫－2－氧）－3，5－环维生素D2。其中BDT（1，3－苯并二硫－2－氧）基团的引入有利于共轭三烯系统的保护。     

(R)-N-乙酰四氢噻唑-2-硫酮-4-羧酸的合成和量子化学研究

（R）－N－乙酰四氢噻唑－2－硫酮－4－羧酸在三乙胺存在下同乙酰氯反应得到光学活性产物（R）－N－乙酰四氢噻唑－2－硫酮－4－羧酸．用半经验的量子化学方法研究反应物及产物的电子结构和反应热焓．     

在H3PO4存在下2,3-二甲基-2-丁烯与乙酐的酰化反应

在H3PO4存在下进行了2，3－二甲基－2－丁烯与乙酐的酰化反应，结果表明，H3PO4是室温下催化2，3－二甲基－2－丁烯与乙酐酰化反应的有效催化剂，在H3PO4存在下，酰化产物的收率主要取决于：（a)H3PO4的用量，（b)乙酐的用量；（c)反应温度和（d)反应时间，在适宜反应条件下，所得3，3，4－三甲基－4－戊烯－2－酮（TMP）约为99％，另外还发现，反应体系中加入少量乙酸，不会明显减少酰化产物的收率，乙酐的纯度，反应物的加入顺序对该反应几乎没有任何影响，在有和没有溶剂CH2Cl2的条件下所得酰化产物的收率是可比的。     

3-(3-吡啶基)-4-氨基-5-芳胺基-1,2,4-三唑的合成与表征

以烟酸与芳胺为基本原料，经多步反应，制得1－烟酰基－4－芳基氨基硫脲；后者在水合肼存在下关环，合成了一系列新化合物3－（3－吡啶基）－4－氨基－5－芳胺基－1，2，4－三唑。化合物结构经元素分析、IR，^1H NMR,^13C NMR确证。     

1,6-二氢-S-四嗪催化重排及其反应的研究--Ⅱ. 与氯甲酸三氯甲酯反应

在4－二甲胺基吡啶的存在下，1，6－二氢－S－四嗪重排成3，6－二氢－S－四嗪，与双光气反应后再与不同的胺反应，合成了11种1，4－二取代产物，产物经元素分析、IR和^1H NMR确证。用UV和^1H NMR分析结果对反应机理进行了初步探讨。     

A general enantioselective approach to jasmonoid fragrances: synthesis of (+)-(1R,2S)-methyl dihydrojasmonate and (+)-(1R,2S)-magnolione

Methyl dihydrojasmonate 1 and magnolione 3 are of both academic and industrial interest. In this paper, we describe a flexible, high-yielding route to diastereomerically pure (+)-cis-(1R,2S)-methyl dihydrojasmonate 1 and the first synthesis of (+)-cis-(1R,2S)-magnolione 3, both with enantiomeric excesses up to 93%. The two syntheses diverged from the same advanced intermediate 5, readily available from the enantioenriched hydroxymethyl delta-lactone (-)-(3aS,4S,6aR)-6. The olfactory properties of (1R,2S)-1 and (1R,2S)-3 are reported.     

Ring currents as probes of the aromaticity of inorganic monocycles : P5-, As5-, S2N2, S3N3-, S4N3+, S4N42+, S5N5+, S42+ and Se42+

Current-density maps were calculated by the ipsocentric CTOCD-DZ/6-311G** (CTOCD-DZ=continuous transformation of origin of current density-diamagnetic zero) approach for three sets of inorganic monocycles: S(4) (2+), Se(4) (2+), S(2)N(2), P(5) (-) and As(5) (-) with 6 pi electrons; S(3)N(3) (-), S(4)N(3) (+) and S(4)N(4) (2+) with 10 pi electrons; and S(5)N(5) (+) with 14 pi electrons. Ipsocentric orbital analysis was used to partition the currents into contributions from small groups of active electrons and to interpret the contributions in terms of symmetry- and energy-based selection rules. All nine systems were found to support diatropic pi currents, reinforced by sigma circulations in P(5) (-), As(5) (-), S(3)N(3) (-), S(4)N(3) (+), S(4)N(4) (2+) and S(5)N(5) (+), but opposed by them in S(4) (2+), Se(4) (2+) and S(2)N(2). The opposition of pi and sigma effects in the four-membered rings is compatible with height profiles of calculated NICS (nucleus-independent chemical shifts).     

Structure and unimolecular chemistry of protonated sulfur betaines, (CH3)2S(+)(CH2)(n)CO2H (n = 1 and 2)

The fixed charge zwitterionic sulfur betaines dimethylsulfonioacetate (DMSA) (CH(3))(2)S(+)CH(2)CO(2)(-) and dimethylsulfoniopropionate (DMSP) (CH(3))(2)S(+)(CH(2))(2)CO(2)(-) have been synthesized and the structures of their protonated salts (CH(3))(2)S(+)CH(2)CO(2)H···Cl(-) [DMSA.HCl] and (CH(3))(2)S(+)(CH(2))(2)CO(2)H···Pcr(-) [DMSP.HPcr] (where Pcr = picrate) have been characterized using X-ray crystallography. The unimolecular chemistry of the [M+H](+) of these betaines was studied using two techniques; collision-induced dissociation (CID) and electron-induced dissociation (EID) in a hybrid linear ion trap Fourier transform ion cyclotron resonance mass spectrometer. Results from the CID study show a richer series of fragmentation reactions for the shorter chain betaine and contrasting main fragmentation pathways. Thus while (CH(3))(2)S(+)(CH(2))(2)CO(2)H fragments via a neighbouring group reaction to generate (CH(3))(2)S(+)H and the neutral lactone as the most abundant fragmentation channel, (CH(3))(2)S(+)CH(2)CO(2)H fragments via a 1,2 elimination reaction to generate CH(3)S(+)=CH(2) as the most abundant fragment ion. To gain insights into these fragmentation reactions, DFT calculations were carried out at the B3LYP/6-311++G(2d,p) level of theory. For (CH(3))(2)S(+)CH(2)CO(2)H, the lowest energy pathway yields CH(3)S(+)=CH(2)via a six-membered transition state. The two fragment ions observed in CID of (CH(3))(2)S(+)(CH(2))(2)CO(2)H are shown to share the same transition state and ion-molecule complex forming either (CH(3))(2)S(+)H or (CH(2))(2)CO(2)H(+). Finally, EID shows a rich and relatively similar fragmentation channels for both protonated betaines, with radical cleavages being observed, including loss of ˙CH(3).     

Terpenes in organic synthesis. 8. Synthesis of optically active (2R/S, 3S, 7R/S)-(-)-diprionyl acetate from (S)-(+)-3,7-dimethyl-1,6-octadiene

Conclusions A seven-stage synthesis has given optically active (2R/S, 3S, 7R/S)-2-acetoxy-3,7-dimethylpentadecane from the readily available (S)-(+)-3,7-dimethyl-1,6-octadiene, in an overall yield of 36%. The synthetic route utilizes all ten carbon atoms of the starting chiral diene.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1142–1146, May, 1988.     

Syntheses of (S)-(+)-trihexyphenidyl hydrochloride and (S)-(+)-procyclidine hydrochloride, two anticholinergics, using (S)-(-)-3-cyclohexyl-3-hydroxy-3-phenylpropanoic acid as chiral synthon

The absolute configuration of the more active (-)-enantiomer of the anticholinergic trihexyphenidyl hydrochloride has been established as (R) by syntheses of (S)-(+)-procyclidine hydrochloride, whose absolute configuration has been established previously, and (S)-(+)-trihexyphenidyl hydrochloride from the same chiral building block, viz. (S)-(-)-cyclohexyl-3-hydroxy-3-phenylpropanoic acid. Both enantiomers of this chiral synthon were prepared by optical resolution of the corresponding racemate, employing (R)- and (S)-1-phenylethylamine, respectively, as resolving agents.     

A Practical Synthesis of (S)-(+)-2-(6-methoxyl-2-naphthyl) propionic Acid

a-Arylpropionic acids are an important class of non-steroidal anti-inflammatory agents1,2. The therapeutic efficacy of this class of drugs is well demonstrated by the introduction and extensive use of more than a dozen compounds exemplified by ibuprofen, naproxen, ketoprofen and flurbiprofen etc. However, in recent years the use of enantiomerical pure drugs in chemotherapy is becoming almost mandatory for enhancing specificity of drug action and reducing the toxicity. This awareness led to …     

Synthesis of the anti-Helicobacter pylori agent (+)-spirolaxine methyl ether and the unnatural (2"S)-diastereomer

The first enantioselective synthesis of the anti-Heliocbacter pylori agent (+)-spirolaxine methyl ether 2b has been carried out in a convergent fashion establishing that the absolute stereochemistry of the natural product is in fact (3R, 2"R, 5"R, 7"R) after initial synthesis of the unnatural (2"S)-diastereomer 2a. The key step in the synthesis of (+)-spirolaxine methyl ether 2b involved a heterocycle-activated Julia-Kocienski olefination between benzothiazole-based spiroacetal sulfone 4b and phthalide aldehyde 3a. (2"R, 5"S, 7"S)-Spiroacetal sulfone 4b was prepared via cyclisation of protected dihydroxyketone 6b, which in turn was derived from the coupling of the acetylide derived from (R)-acetylene 24b with aldehyde 3a. Phthalide aldehyde 3a was prepared via intramolecular acylation of bromocarbamate 15, which was available via titanium tetrafluoride-(+)-BINOL-mediated allylation of 3,5-dimethoxybenzaldehyde 13. Union of the sulfone 4b and aldehyde 3a fragments successfully completed the enantioselective synthesis of (+)-spirolaxine methyl ether 2b. The synthesis of the unnatural (3R, 2"S, 5"R, 7"R)-diastereomer of spirolaxine methyl ether 2a was also undertaken in a similar manner by union of phthalide aldehyde 3a with (2"S, 5"S, 7"S)-spiroacetal sulfone 4a derived from (S)-acetylene 24a.     

手性3,7-二甲基-5,6-二羟基-辛-7-烯醛中间体的合成

以天然长叶薄荷酮[R-(+)-Pulegone]为起始原料,经过一系列立体选择性化学反应步骤,成功地建立了3个手性中心,从而完成了具有抗艾滋病活性Didemnaketals类似物的关键中间体3,7-二甲基-5,6-二羟基-辛-7-烯醛中间体的合成.发现PCC与三级环氧醇8和9的非对映选择性反应,使得9被完全氧化,而8以93%的产率回收,其de值高达98%.     

An efficient procedure for the preparation of (1S,3R)- and (1S,3S)-1-amino-3-(hydroxymethyl)cyclopentanes

Enantiomerically pure (1S,3S)- and (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentanes have been efficiently synthesized from L-aspartic acid. The title compounds are isosteres of ribose and may be used to construct nucleoside analogs with important antiviral and antineoplastic activities as demonstrated by a concise total synthesis of (+)-4'-deoxycarbapentostatin nucleoside.