Studies toward the synthesis of pinolidoxin, a phytotoxic nonenolide from the fungus Ascochyta pinodes. Determination of the configuration at the C-7, C-8, and C-9 chiral centers and stereoselective synthesis of the C(6)-C(18) fragment

The absolute stereochemistry at the C-7, C-8, and C-9 chiral centers of pinolidoxin (1) has been determined by chemical and spectral methods. First, the synthesis of four stereoisomeric fully benzoylated 2,3-erythro-1,2,3,4-heptanetetrols, corresponding to the C(6)-C(18) portion of the natural substance, has been accomplished starting from meso-tartaric acid. As next step, the selection of the synthetic tetrabenzoate possessing "natural" stereochemistry (10a'), suitable for absolute configuration determination, has been carried out by correlation with its "natural" homologue derived from degradation of pinolidoxin. Determination of the stereochemistry at the title chiral centers has been carried out by application of the Mosher's method both to 7a', a compound stereochemically related to 10a', and to pinolidoxin itself. The stereoselective synthesis of a protected form of the C(6)-C(18) portion of pinolidoxin, to be used in its total synthesis, has also been accomplished starting from commercially available D-erythronolactone.     

Synthesis of dihydroarbiglovin and stereochemistry of arbiglovin*

Dihydroarbiglovin (III) has been synthesized by a stereoselective route starting with photolysis of santonin. The synthesis determines the stereochemistry at C-1 and C-10 as shown for arbiglovin (I).     

Polymethine dyes based on pyrroloanthrone

Pyrroloanthrone has been used as the starting material in the synthesis of 6-methylthionaphthindolinium salts that were used in turn to obtain polymethine dyes. The dependence of the color of the cyanines on their chemical structure has been analyzed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1413–1420, October, 1990.     

First enantioselective total synthesis of (8S,12R,15S)-prostaglandin J(2)

Enantioselective synthesis of natural PGJ(2) has been accomplished for the first time starting from the commercially available enantiopure aldehyde 7 in 10% overall yield. The key reaction was a novel prostaglandin class interconversion, i.e., an allylic 1,3-transposition across alcohol 9 derived from compound 14 in 73% overall yield. In principle, the unnatural enantiomer of PGJ(2) could be obtained starting from the commercially available enantiopure monobenzoate 7a following our strategy.     

A simple and efficient stereoselective synthesis of (−)-cleistenolide

A simple and straightforward stereoselective synthesis of α,β-unsaturated δ-lactone, (?)-cleistenolide has been accomplished in 10 steps in an overall yield of 19%, starting from inexpensive and commercially available starting materials, respectively. This linear synthesis utilizes Sharpless asymmetric dihydroxylation, sulfur ylide mediated epoxide opening followed by ring-closing metathesis (RCM) for the formation of six-membered lactone ring as the key step sequence.     

Rapid and Large-Scale Synthesis of Sulfonyl-Substituted Propanones

A one-pot, large-scale, and rapid (10–20 minutes) synthesis of sulfonyl-substituted propanones has been developed. The synthesis, starting with a thiol, chloroacetone, and OXONE. can easily be monitored with the use of a pH indicator.     

Organocatalytic enantioselective synthesis of highly functionalized polysubstituted pyrrolidines

The organocatalytic conjugate addition of different aldehydes to beta-nitroacrolein dimethyl acetal, generating the corresponding highly functionalized nitroaldehydes in high yields and with high stereoselectivities, has been studied in detail. These transformations have been achieved by using both readily available starting materials in a 1:1 ratio as well as commercially available catalysts at a 10 mol % catalyst loading. Furthermore, a very short and efficient protocol has been devised for the preparation of highly enantioenriched pyrrolidines containing two or three contiguous stereocenters starting from the obtained Michael adducts. 3,4-Disubstituted pyrrolidines have been obtained in a single step by Zn-mediated chemoselective reduction of the nitro group followed by intramolecular reductive amination, and trisubstituted homoproline derivatives have been prepared by means of an olefination reaction and a cascade process involving chemoselective reduction of the nitro group followed by a fully diastereoselective intramolecular aza- Michael reaction.     

大环二萜天然产物(±)-Mayol的全合成

西松烷型二萜类化合物是一大类广泛分布于松脂、烟草、陆地动物及海洋生物体中的具有十四元碳环骨架的化合物.其结构新颖复杂,且大多具有显著和广谱的生物活性.近几十年来,有关这类化合物的研究已引起了人们的极大兴趣.因此,开展这类天然产物及其类似物的全合成及构效关系的研究不仅具有重要的学术价值,而且具有潜在的应用前景.     

Total syntheses of four stereoisomers of 4alpha-hydroxy-1beta,7beta-peroxy- 10betaH-guaia-5-ene

[reaction: see text]. The first total syntheses of four stereoisomers of 4alpha-hydroxy-1beta,7beta-peroxy-10betaH-guaia-5-ene are reported starting from the readily available (+)-dihydrocarvone. These compounds have been synthesized from dienes (-)-isoguaiene and (-)-10-epi-isoguaiene by tandem ene hydroperoxylation-[4 + 2] cycloaddition with O(2) followed by selective reduction. The structure of the natural 4alpha-hydroxy-1beta,7beta-peroxy-10betaH-guaia-5-ene isolated from Liabum floribundum has been confirmed.     

Stereoselective and facile total synthesis of (+)-goniodiol,a styryllactone from carbohydrates

The stereoselective synthesis of (+)-goniodiol, a cytotoxic styryllactone, has been accomplished in 10 steps starting from inexpensive and readily available d-manitol and δ-gluconolactone involving the direct and straightforward reaction conditions of Grignard addition, chain elongation, and hydroboration, thus making the synthesis simple and convenient.     

A New,Stereoselective Approach to the [3.3.3]Propellane System: Synthesis of (±)-modhephene. Preliminary communication

The unusual propellane skeleton of the sesquiterpene modhephene ( 1 ) has been synthesized starting from cyclopentenone ( 2 ). The key step 6 → 7 is an efficient and highly stereoselective intramolecular thermal ene-reaction. Further elaboration of the propellane 7 gave the enone 10 which had been previously converted to (±)-modhephene ( 1 ) in three steps.     

Model experiments on surugatoxin synthesis. an approach in the construction of the pentacyclic ring system

Synthesis of the ethyl ester 2a of the debromo-aglycone of surugatoxin 1 has been achieved in 10 steps starting from readily available ethyl 2-(2-oxo-3-indolenyl)-3-oxo-4-phthalimidobutyrate 3.     

Syntheses of 9-Triptycylisothiocyanate, (10-Amino-9-triptycyl)carboxylic Acid,and Their Derivatives

In the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 9-triptycylisothiocyanate has been synthesized in 91% yield from carbon disulfide and sterically hindered 9-triptycylamine at room temperature. 9-Triptycylisothiocyanate can be further converted to 1-benzyl-3-(9-triptycyl)thiourea. (10-Amino-9-triptycyl)carboxylic acid has also been successfully synthesized via a three-step route starting from methyl 10-nitroanthracene-9-carboylate. Its amino and carboxylic groups can undergo acetylation and amidation, respectively.     

新型植物生长调解剂1-甲基-3-氧乙酸吲唑的合成和应用

植物生长调解剂;吲唑衍生物;新型植物生长调解剂1-甲基-3-氧乙酸吲唑的合成和应用     

Synthesis of 2-(1-methyl-4-piperylid-3-ene)-9,10-dihydro-4H-benzo[4,5]- cyclohepta[1,2-b]thiophen-10-one,a new potential antiasthmatic analogue of zaditene

The title compound has been prepared in four steps from readily available starting material. The key reaction is the metallation of 10-methoxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophene, which occurs exclusively at the desired 2 position.     

Acid-catalyzed acetylation of N-methallyl lactam and imide derivatives

The reactions of N-methallyl derivatives of cyclic amides and imides with acetic and propionic anhydride have been studied in the presence of perchloric acid. The reaction products have been found to be pyrylium and oxazolinium salts. The relationship between the reaction pathway and the structure of the imide or amide starting material has also been determined. Pyrylium salts have been converted to their corresponding pyridine bases.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1414–1419, October, 1988.     

C10-substituted camphors and fenchones by electrophilic treatment of 2-methylenenorbornan-1-ols: enantiospecificity,scope, and limitations

Valuable chiral sources of C(10)-substituted camphors and C(10)-substituted fenchones can be straightforwardly obtained by treatment of an appropriate, easily obtainable, camphor- or fenchone-derived 2-methylenenorbornan-1-ol with an electrophilic reagent. The process takes place via a tandem regioselective carbon-carbon double-bond addition/stereocontrolled Wagner-Meerwein rearrangement. A complete study of the enantiospecificity, scope, and limitations of this process, as well as about the role played by the hydroxyl group attached at the C(1) bridgehead position of the starting 2-methylenenorbornan-1-ols, has been realized. The feasibility of the described methodology has been exemplified by the highly efficient enantiospecific preparation of several interesting C(10)-halogen-, C(10)-O-, C(10)-S-, C(10)-Se-, or C(10)-C-substituted camphors and fenchones.     

Efficient access to isomeric 2,3-dihydroxy lupanes: first synthesis of alphitolic acid

Alphitolic acid (3) is a naturally occurring lupane type of pentacyclic triterpene, which possesses various pharmacological properties. Efficient synthesis of 3 has been accomplished in 10 steps with an overall yield of 19% starting from the readily available diketone 11. An alternative approach to the key intermediate 17 has also been developed, and based on this approach, 3 could be obtained in 10 steps with an overall yield of 26% starting from 11. Moreover, seven other isomeric 2,3-dihydroxy lupanes 4-10 have been synthesized. The synthesized triterpenes 3-10 were evaluated for their inhibitory activity against rabbit muscle GPa (RMGPa), and some of them exhibited moderate inhibitory activity against RMGPa.     

Semisynthesis and biological evaluation of a novel D-seco docetaxel analogue

[reaction: see text] A 4-methyl-5-oxo docetaxel analogue has been prepared starting from 10-deacetylbaccatin III. This new D-seco docetaxel analogue is slightly less potent than docetaxel at microtubule stabilization in vitro and has about 1/1000th the cytotoxicity of docetaxel. The lack of improved activity for this compound compared to other D-modified taxoids confirms that a C-5 oxygen atom is not required for biological activity.     

Stereoselective synthesis of 7,11-guaien-8,12-olides from santonin. Synthesis of podoandin and (+)-zedolactone A

Photochemical rearrangement of hydroxy ester 2, easily obtained from santonin (1), afforded butenolide 4, a good starting material for the synthesis of 7,11-guaien-8,12-olides. Compound 4 has been transformed into compound 10, which has been used for the synthesis of podoandin (5) and (+)-zedolactone A (ent-6). Regioselective elimination of the acetyl group on C10 afforded directly podoandin (5). For the synthesis of ent-6, a hydroxyl group has been regio- and stereoselectively introduced at the 4alpha-position through the 3alpha,4alpha-epoxide 15. The basic hydrolysis of the 10-acetyl group in compound 18 took place with concomitant intramolecular conjugated addition of the alkoxide to the butenolide moiety to give ether 19. Cleavage of the 7,10-oxido bridge via the lactone enolate afforded (+)-zedolactone A (ent-6). This synthesis has allowed for the establishment of the absolute stereochemistry of natural zedolactone A as the enantiomer of our synthetic product.