The carbazole-3,4-quinone alkaloids, carquinostatin A (1) 1) and lavanduquinocin (2) 2) were isolated from Streptomyces exfoliates 2419-SVT2 and Streptomyces viridochromogenes by Seto and co-workers in 1993 and 1995, respectively. The structures of the two alkaloids were elucidated to be the same carbazole-3,4-quinone moiety by NMR spectral analyses and other spectroscopic experiments. The absolute stereochemistry of the C-11 position of the two alkaloids was the same R-configuration. Carquinostatin A (1) and lavanduquinocin (2) were also shown to be a potent neuronal cell protecting substance which exhibits a free radical scavenging activity. Total syntheses of these alkaloids have recently been developed by the Knölker group. [3][4][5][6][7][8] The transition metalmediated and -catalyzed methodologies for the construction of the carbazole framework have been efficiently employed.Throughout the course of this study, we have been interested in the synthetic development of biologically active condensed-heteroaromatic compounds, including natural products, by the thermal electrocyclic reactions of either conjugated hexatriene [9][10][11][12][13][14][15][16][17] or monoazahexatriene 18) systems incorporating one double bond from an aromatic or heteroaromatic portion. We recently reported the synthesis of the highly substituted carbazole alkaloids, carazostatin 9) and carbazoquinocins, 9,10) by the construction of the appropriate carbazole framework based on the allene-mediated electrocyclic reaction of the 6p-electron system involving the indole 2,3-bond. In the present paper, we describe the asymmetric synthesis of 6-desprenyl-carquinostatin A (6-descycloavandulyllavanduquinocin) 3, which is a common carbazole framework of both alkaloids, based on a lipase-catalyzed esterification using a racemic alcohol 6 for the determination of the absolute stereochemistry of 3. We chose the 3-ethoxy-2-methyl-1-(trifluoromethylsulfonyloxy)carbazole (4), 9,10) as a starting material, which was prepared in a six-step sequence from 3-iodoindole-2-carbaldehyde by the application of our methodology, as shown in the retrosynthetic Chart 1.The required 1-allylcarbazole 5 was prepared from the triflate 4 and allyboronic acid pinacol ester in the presence of PdCl 2 (dppf) in dimethylformamide (DMF) by the SuzukiMiyaura reaction. 19,20) An asymmetric synthesis of the core carbazole structure, 6-desprenyl-carquinostatin 3 and 6-descycloavandulyl-lavanduquinocin 3, toward a total synthesis of carquinostatin A (1) and lavanduquinocin (2)
Total syntheses of ( )-carquinostatin A (1), and (R)-( )-carquinostatin A (1a) together with its enantiomer, (S)-( )-carquinostatin A (1b), possessing radical scavenging activity, were newly achieved. ( )-Carquinostatin A (1) was synthesized from 1-acetonyl-6-bromo-3-ethoxy-2-methylcarbazole (6), which was derived from the known 1-acetonyl-3-ethoxy-2-methylcarbazole (5). Introduction of a prenyl group at the 6-position of carbazole was successful in two steps. For the synthesis of (R)-( )-carquinostatin A (1a) and (S)-( )-carquinostatin A (1b), (R)-( )-1-(2-acetoxypropyl)-3-hydroxy-2-methylcarbazole (15a) and (S)-( )-3-hydroxy-1-(2-hydroxypropyl)-2-methylcarbazole (15b), prepared by lipase-QLM catalyzed enantioselective transesterification of 3-hydroxy-1-(2-hydroxypropyl)-2-methylcarbazole (14), were used as the chiral starting material.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.