Enantioselective Synthesis of (+)-Malbrancheamide B

Abstract

The asymmetric total synthesis of the chlorinated [2.2.2]-diazabicyclic indole alkaloid (+)-malbrancheamide B is reported. Key to the synthesis is a domino reaction sequence that employs an aldol condensation, alkene isomerization, and intramolecular Diels-Alder cycloaddition. Diastereofacial selection between the azadiene stereofaces is enforced with a chiral aminal auxiliary. A formal 7-step (longest linear route) synthesis of (±)-malbrancheamide B is also reported.

Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C–N Bonds in Total Synthesis

“…As a part of a combined synthetic/biosynthetic program aimed at pursuing Diels–Alder-ase, an elusive putative enzyme catalyzing biosynthetic Diels–Alder reactions, the Williams group described a series of total synthesis accomplishments in the area of prenylated indole alkaloids containing a bicyclo[2.2.2]­diazaoctane core. − This diverse group of alkaloids is isolated from both terrestrial and marine fungi. The total synthesis of (+)- and (−)-versicolamides B from fungi of the Aspergillus genus serve as an example .…”

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…The diastereofacial selectivity of azadiene 210 in the cycloaddition step was effectively controlled by the chiral aminal auxiliary (Scheme 51). 91 A new carbazole alkaloid, antipathine A (210), was isolated from the South China Sea black coral Antipathes dichotoma in 2009, and its structure was originally postulated to be 211. The rst total synthesis of 210 was achieved using Pd-catalyzed Buchwald-Hartwig coupling and Pd-mediated oxidative coupling to install the carbazole framework.…”

The Complete Mechanism of an Aldol Condensation

“…There are many variants, including the Claisen, Dieckmann, Henry, and Darzens condensations and the Knoevenagel and Perkin reactions. Because of their ability to construct larger molecules from smaller ones, − or to effect cyclization, − often with control of stereochemistry, − these reactions are a mainstay of organic synthesis. They are also common in metabolism, where aldolase, citrate synthase, and other enzymes catalyze aldol reactions and aldol condensations, or their reverse, leading to the suggestion that they reflect primordial metabolism. , …”