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Regiospecific, enantiospecific total synthesis of C-19 methyl substituted sarpagine alkaloids dihydroperaksine-17-al and dihydroperaksine.

ABSTRACT: The optically active tetracyclic ketone 8 was converted into the pentacylic core 14 of the C-19 methyl substituted N(a)-H sarpagine and ajmaline alkaloids via a critical haloboration reaction. The ketone 14 was then employed in the total synthesis of 19(S),20(R)-dihydroperaksine-17-al (1) and 19(S),20(R)-dihydroperaksine (2). The key regioselective hydroboration and controlled oxidation-epimerization sequence developed in this approach should provide a general method to functionalize the C(20)-C(21) double bond in the ajmaline-related indole alkaloids.

SUBMITTER: Edwankar RV

PROVIDER: S-EPMC3184356 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Regiospecific, enantiospecific total synthesis of C-19 methyl substituted sarpagine alkaloids dihydroperaksine-17-al and dihydroperaksine.

Edwankar Rahul V RV Edwankar Chitra R CR Deschamps Jeffrey J Cook James M JM

Organic letters 20110830 19

The optically active tetracyclic ketone 8 was converted into the pentacylic core 14 of the C-19 methyl substituted N(a)-H sarpagine and ajmaline alkaloids via a critical haloboration reaction. The ketone 14 was then employed in the total synthesis of 19(S),20(R)-dihydroperaksine-17-al (1) and 19(S),20(R)-dihydroperaksine (2). The key regioselective hydroboration and controlled oxidation-epimerization sequence developed in this approach should provide a general method to functionalize the C(20)-C ...[more]

PMID: 21877687

Similar Datasets

General strategy for synthesis of C-19 methyl-substituted sarpagine/macroline/ajmaline indole alkaloids including total synthesis of 19(S),20(R)-dihydroperaksine, 19(S),20(R)-dihydroperaksine-17-al, and peraksine.

Project description:A detailed account of the development of a general strategy for synthesis of the C-19 methyl-substituted alkaloids including total synthesis of 19(S),20(R)-dihydroperaksine-17-al (1), 19(S),20(R)-dihydroperaksine (2), and peraksine (6) is presented. Efforts directed toward the total synthesis of macrosalhine chloride (5) are also reported. Important to success is the sequence of chemical reactions which include a critical haloboration reaction, regioselective hydroboration, and controlled oxidation (to provide sensitive enolizable aldehydes at C-20). In addition, the all-important Pd-catalyzed α-vinylation reaction has been extended to a chiral C-19 alkyl-substituted substrate for the first time. Synthesis of the advanced intermediate 64 completes an improved formal total synthesis of talcarpine (26) and provides a starting point for synthesis of macroline-related alkaloids 27-31. Similarly, extension of this synthetic strategy in the ring A oxygenated series should provide easy access to the northern hemisphere 32b of the bisindoles angustricraline, alstocraline, and foliacraline (Figure 4 ).

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Project description: Not available

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Completion of the Total Synthesis of Several Bioactive Sarpagine/Macroline Alkaloids including the Important NF-κB Inhibitor N4-Methyltalpinine.

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Enantiospecific total synthesis of N-methylwelwitindolinone D isonitrile.

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Unified Total Synthesis of the Limonoid Alkaloids: Strategies for the De Novo Synthesis of Highly Substituted Pyridine Scaffolds.

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Three-component coupling sequence for the regiospecific synthesis of substituted pyridines.

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