Blocking group-directed diastereoselective total synthesis of (±)-α-noscapine

A new approach for the diastereoselective synthesis of (±)-α-noscapine, a phthalide tetrahydroisoquinoline alkaloid exhibiting several biological activities, is described. The strategy features a blocking group-directed Bischler-Napieralski reaction followed by diastereoselective reduction (α/β>23:1). One of the key intermediates, phthalide-3-carboxylic acid, could be efficiently prepared from simple benzoic acid derivative and glyoxylic acid in one-pot.     

Stereoselective syntheses of γ-alkyl (aryl)-α,β-dihydroxy-γ-butyrolactones and naturally occurring lipid guggultetrol

γ-Oxo-butyramides derived from tartaric acid serve as excellent precursors for the synthesis of γ-alkyl (aryl)-α,β-dihydroxy-γ-butyrolactones and for the synthesis of tetrols containing three contiguous stereogenic centres. The methodology presented here is general for the synthesis of γ-alkyl (aryl)-α,β-dihydroxy-γ-butyrolactones. Utility of the chiral building block was demonstrated by the synthesis of naturally occurring lipid guggultetrol.     

Stereospecific total syntheses of 7α- and 7β-eremophilane-6-one and 7α- and 7β-eremophilane

The title compounds have been prepared in a highly efficient fashion by a synthetic route involving an intramolecular Diels-Alder reaction of an acetylenic thiazole followed by reductive modification of the resulting fused-ring thiophene.     

Stereoselective syntheses of (+)-α- and (−)-β-conhydrine from L-aspartic acid

An efficient synthesis of (+)-α-conhydrine 1 and (−)-β-conhydrine 2 has been achieved by diastereoselective alkylation of an amino aldehyde derivative 7 with ethylmagnesium bromide or diethylzinc.     

Concise syntheses of substituted indolizidine alkaloids via cyclization based on α-sulfinyl carbanions: preparation of (±)-indolizidines 167B and 209D, their epimers, and (±)-tashiromine

(±)-Indolizidines 167B and 209D, their epimers and (±)-tashiromine have been successfully synthesized, starting from simple γ- or α-lactams. The strategy involves the cyclization of α-sulfinyl carbanion onto the carbonyl group of the lactam ring as the key step, leading to the indolizidines containing the phenylsulfinyl group, which are used as precursors for the preparation of the title compounds.     

Scalable, stereocontrolled total syntheses of (±)-axinellamines A and B

The development of a simple, efficient, scalable, and stereocontrolled synthesis of a common intermediate en route to the axinellamines, massadines, and palau'amine is reported. This completely new route was utilized to prepare the axinellamines on a gram scale. In a more general sense, three distinct and enabling methodological advances were made during these studies: (1) an ethylene glycol-assisted Pauson-Khand cycloaddition reaction, (2) a Zn/In-mediated Barbier-type reaction, and (3) a TfNH(2)-assisted chlorination-spirocyclization.     

Stereocontrolled total synthesis of (±)-3β-hydroxy-9β-pimara-7,15-diene, a putative biosynthetic intermediate of momilactones

The total synthesis of (±)-3β-hydroxy-9β-pimara-7,15-diene (1), a putative biosynthetic intermediate of the momilactones, was accomplished stereoselectively. Our methodology for the synthesis of 1 featured the stereoselective construction of the C-13 quaternary carbon center via the aldol-Tishchenko reaction. 3β-Hydroxy-9β-pimara-7,15-diene (1) was identified by full-scan GC-MS analysis as an endogenous compound in elicited rice cells.     

An expedient total synthesis of optically active piperidine and indolizidine alkaloids (−)-β-conhydrine and (−)-lentiginosine

Attempts directed toward the stereocontroled total synthesis of piperidine and indolizidine alkaloids resulted in the synthesis of (−)-β-conhydrine 1 and (−)-lentiginosine 3. The synthesis of 1 and 3 were developed from protected d-mannitol as the chiral precursor, which involved nucleophilic addition and azide nucleophilic substitution, Barbier allylation, ring closing metathesis, and Sharpless asymmetric dihydroxylation as the key steps.     

天然产物(±)-Lupinine和(±)-Epilupinine的简便合成

羽扇豆碱和表羽扇豆碱是典型的喹诺里西啶类生物碱。以哌啶酸乙酯盐酸盐为原料,通过氮烷基化反应、迪克曼缩合反应、Krapcho脱羰反应、Wittig反应等4步反应制得关键中间体5,总产率46.7%。化合物5可经文献转化,完成(±)-lupinine和(±)-epilupinine的合成。该合成方法具有合成路线短,产率高以及操作简单等优点。      

螺环倍半萜(±)-茅苍术醇和(±)-沉香螺醇的改进合成

以2,4-二氧代戊酸甲酯(1)和1,5-二甲基-6-亚甲基环己烯(2)为原料,通过[2+2]光环加成和retro-Benzilicacid重排,合成了具有螺[4,5]癸烷结构的岩兰烷基本碳架的化合物3.用锌粉选择还原五元环上碳碳双键得螺环二酮(4),对环外羰基实施保护并将环上酮基转化为亚甲基得到重要的合成前体6,经与甲基溴化镁的格氏反应生成混合的标题化合物.利用羟基和异氰酸苯酯的反应生成一对N-苯基氨基甲酸酯异构体(12),二者分离后经四氢铝锂还原,完成了螺环倍半萜(±)-茅苍术醇和(±)-沉香螺醇的全合成.     

A total synthesis of (±)-α-cyclopiazonic acid using a cationic cascade as a key step

The indole alkaloid α-cyclopiazonic acid 1 has been synthesised by a route, which features at its core an acid-catalysed cationic cascade cyclisation terminated by a sulfonamide group.     

A facile stereoselective synthesis of (Z)-α-arylsulfonyl-α,β-unsaturated ketones

Palladium-catalyzed hydrostannylation of acetylenic sulfones 1 in benzene at room temperature gives highly regio- and stereoselectively (E)-α-stannylvinyl sulfones 2 in high yields. (E)-α-Stannylvinyl sulfones 2 are new difunctional group reagents which undergo Stille coupling reactions with acyl chlorides 3 to afford stereoselectively (Z)-α-arylsulfonyl-α,β-unsaturated ketones 4 in good yields. A one-pot stereoselective synthesis of (Z)-α-arylsulfonyl-α,β-unsaturated ketones 4 has also been achieved by tandem hydrostannylation-Stille coupling reaction of acetylenic sulfones 1 under mild conditions.     

Convergent total syntheses of callipeltosides a, B, and C

Going for the hat-trick: The synthesis of the entire callipeltoside family of natural products is described. Key to this synthesis was the coupling of the di-ene-yne and pyran fragments by a diastereoselective alkenylzinc addition allowing rapid access to the common aglycon. Attachment of each relevant L-configured sugar resulted in the first total synthesis of callipeltoside B, and the syntheses of callipeltosides?A and C.     

Stereoselective total synthesis of (±)-peribysin E

Radical cyclization of iodoketone 3 afforded cis-hydrindanone 8. Compound 8 was converted into key intermediate 5 via conventional transformations. Annulation of a spiro-lactal unit to 5 was pursued with three different approaches. In the first approach, radical cyclization of propargyl ester 17 provided spiro-lactone 18 with an undesired stereochemistry. Attempts to invert the stereochemistry at the spiro-center via retro-aldol and aldol condensation of compound 20 failed. In the second approach, key intermediate 5 was transformed into 23. Acylation of compound 23 gave 24 as a single diastereomer with the desired stereochemistry but in low yield. NBS bromination of 24 followed by lactone formation gave 26 in low yield. Alternatively, allylic oxidation of 24 with SeO(2) followed by lactonization gave 26 also in low yield. Finally, a third approach employing a semipinacol-type rearrangement of epoxy-alcohol 33 gave aldehyde 34 with the desired stereochemistry. Treatment of compound 34 with HCl in MeOH effected spiro-lactal formation and provided (±)-peribysin E. The overall yield of our synthesis is 3.2% from 2-methylcyclohenen-1-one.     

Tandem Reaction of Deprotonation-Oxidation-Wittig Reaction: Stereoselective Synthesis of (E)-α,β-Unsaturated Enoates

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Stereoselective synthesis of 2-(α-hydroxyalkyl)benzimidazoles

Lithiated oxazolo[3,4-a]benzimidazole 4 reacted with various alkyl halides to give oxazolo[3,4-a]benzimidazoles 5a–d in good yields as single diastereoisomers. (R)-Benzimidazol-2-yl carbinols 6a–d were obtained upon hydrolysis under acidic conditions of 1H,3H-oxazolo[3,4-a]benzimidazole derivatives.