Lewis Acid‐Assisted Ene Cyclization of 2‐Azetidinone‐Tethered Enals: Synthesis of Enantiopure Carbacepham Derivatives

Diastereocontrolled Lewis acid‐catalyzed preparation of enantiopure carbacepham derivatives have been developed starting from 2‐azetidinone‐tethered enals. The BF₃?Et₂O‐promoted reaction of alkenylaldehydes 1 and 16 is effective as carbocyclization protocol to afford 4‐substituted 5‐hydroxycarbacephams or 3‐substituted 4,5‐dihydroxycarbacephams, respectively, by a type I carbonyl‐ene reaction, while the BF₃?Et₂O or SnCl₄‐mediated type II carbonyl‐ene cyclization of alkenylaldehydes 2 furnishes 3‐methylene 5‐hydroxycarbacephams along with the corresponding 3‐halo 5‐hydroxycarbacepham. The stereochemical outcome of these carbonyl‐ene cyclizations leading to carbacepham derivatives can be explained in terms of six‐membered, cyclic chair‐like transition‐state models. The formation of halocarbacepham derivatives is proposed to proceed by a stepwise mechanism.     

Substituent effect on diastereoselectivity in Type-II ene cyclisation: a theoretical study

Methyl and methoxy substituted transition states (TS) of Type-II ene cyclisation have been optimized by ab-initio method and relative stability of the diastereomeric TSs have been calculated. In all TSs, equatorial substituent positions have been found to be preferred over the axial positions except for the 4′-substituted methoxy derivative, in which the methoxy group prefers to retain axial position. It has also been noted that the presence of the methoxy group(s) in other position(s) may affect the stability of axially oriented TS and thus alters the overall stereoselectivity of the reaction.     

Total synthesis of the mushroom metabolite (+)-calopin

A synthesis of (+)-calopin (1a) was achieved employing a highly stereoselective ene reaction between 8-phenylmenthyl glyoxylate (3) and the β,β-dimethylstyrene 4c. Transesterification of the resulting homoallylic alcohol 5c, followed by allylic oxidation and hydrogenation yielded the δ-lactone 13 which was deprotected to the natural product 1a.     

Synthesis of a transmembrane ionophore based on a C2-symmetric polyhydroxysteroid derivative

The synthesis of the C₂-symmetric bis-(20S)-5α-23,24-bisnorchol-16-en-3β,6α,7β-triol-22-terephthaloate (1), active as Na⁺-transporting transmembrane channel, has been achieved in 16 steps (10% overall yield) starting from the commercially available androst-5-en-3β-ol-17-one (3). The straightforward stereospecific functionalization of the side-chain, via the ‘ene’ reaction, and the successful regioselective terephthaloylation of the C-22 hydroxy group, illustrate the efficiency of the synthetic strategy.     

Detection of androst-4-ene-3,6,17-trione (6-OXO) and its metabolites in urine by gas chromatography-mass spectrometry in relation to doping analysis

The metabolism and excretion of androst-4-ene-3,6,17-trione after administration of the 'nutritional' supplement 6-OXO was investigated by gas chromatography-mass spectrometry (GC-MS) in full-scan mode. The parent drug androst-4-ene-3,6,17-trione and androst-4-ene-6alpha,17beta-diol-3-one and androst-4-ene-6alpha-ol-3,17-dione were detected in the post-administration urine samples. Because androst-4-ene-3,6,17-trione is an anabolic steroid and an aromatase inhibitor, this substance is regarded as a doping agent. Hence, a selective and sensitive GC-MS method in selected ion monitoring mode for the detection of the TMS-enol-TMS-ether derivatives of these substances was developed and validated for doping control purposes. The limit of detection (LOD) of the investigated compounds ranged from 5 to 10 ng/mL. Using this method, the detection time for androst-4-ene-3,6,17-trione and androst-4-ene-6alpha,17beta-diol-3-one was 24 h, while androst-4-ene-6alpha-ol-3,17-dione could be detected up to 37 h after administration of the dose recommended by the manufacturer.     

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％．     

1,8‐Diazabicyclo[5.4.0]undec‐7‐ene: A Remarkable Base in the Debromination of 4‐ or 5‐Substituted N‐Benzyl α‐Bromo‐α‐p‐Toluenesulfonylglutarimide

Debromination of N‐benzyl 4‐ or 5‐substituted α‐bromo‐α‐p‐toluenesulfonylglutarimides is achieved with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) to give the N‐benzyl 4‐ or 5‐substituted α‐p‐toluenesulfonylglutarimides. The DBU/THF system is applied to a new methodology for the synthesis of bicyclic glutarimide skeleton in moderate yields.     

Chemical transformation of inocalophyllins, preparation of novel pyranocoumarines inocalocyclides

Lactonization of inocalophyllins A (5) and B (6) with toluenesulfonic acid has yielded four novel pyranocoumarins, designated inocalocyclides A-D (1-4). This reaction involved a rare elimination of an isoprene unit and an ene cyclization.     

微乳液毛细管电动色谱烷基苯的保留行为

以阴离子表面活性剂十二烷基硫酸纳（SDS）和阳离子表面活性剂十六烷基三甲基溴化铵（CTMAB）组成的微乳液体系为分离介质,研究一组烷基苯同系物的毛细管电动色谱分离,较系统地考察了多种微乳液条件下溶质的保留时间,容量因子和电动色谱时间窗。结果表明,在SDS组成的微乳液体系中,烷基苯同系物的logk′与烷基链碳数(C=0～5)呈良好线性关系,logk′=aC+b,r＞0.9921。微乳液组成的变化对两种体系的电动分离有不同的影响规律,并对作用机理进行了探讨。