Current Organic Chemistry - Volume 4, Issue 2, 2000

The isolation, structure determination and biological evaluation of the eudistomin alkaloids, isolated mainly from marine tunicates of the genus Eudistoma, is described. The compounds are placed in a well defined unique structural class based upon biogenic considerations. The methods which have been employed towards total synthesis of these metabolites are reviewed in detail.

Porphyrins, usually as metal complexes of either iron or magnesium, are widely distributed in nature, and exist as the prosthetic groups in a wide variety of primary metabolites such as hemoglobins, myoglobins, cytochromes, catalases, peroxidases, chlorophylls, and bacteriochlorophylls. This article describes the current best methodology for preparation of simple, symmetrical model porphyrins, as well as more complex protocols for preparation of unsymmetrically substituted porphyrin systems similar to those found in nature. Basic chemical reactivity of porphyrin and metalloporphyrin systems are then described systematically, using a reactivity profile approach. The discussion of reactivity includes newer developments in this field, focussing on electrophilic and nucleophilic reactions, oxidation, reduction, cycloaddition reactions and intramolecular cyclizations. Using the reactivity profiles presented, porphyrin systems can be functionalized and transformed into novel arrays and systems, and these are providing valuable contributions to catalytic, electron transport, biological and medicinal chemistry.

The Pummerer rearrangement has been widely studied and has received considerable attention as a synthetically useful process. a-Acyl thionium ions generated from a-acyl sulfoxides under Pummerer conditions are powerful electrophiles, reacting efficiently with nucleophilic carbon species. Bimolecular addition of the cation to various carbon-carbon double bonds is well known. In the realm of natural product synthesis, most success has been achieved using intramolecular Friedel-Crafts cyclization of the Pummerer thionium ion intermediate. Interception of the Pummerer intermediate by heteronucleophiles represents an extremely important variation which has been used for the synthesis of numerous nitrogen containing heterocycles. The present article also describes various applications of the domino Pummerer (slash) N-acyliminium ion cyclization cascade. The successful synthesis of a number of alkaloids by this sequence of reactions reveals the usefulness and importance of this unique domino cascade.

We describe how pyrrole derivatives derived from naturally occurring a-amino acids, and β-amino acids prepared from aspartic acid, can be efficiently converted into enantiomerically pure indolizidines by application of a three-part method. First, an optically pure, correctly substituted amino acid is condensed with tetrahydro-2,5-dimethoxyfuran to give the corresponding 1-pyrrolylacetic acid derivative. Second, through the intermediacy of a diazoketone, an alkylated bicyclic pyrrole-cyclohexanone is created by Rh2(OAc)4-catalyzed decomposition to the carbenoid which inserts into the a-position of the pyrrole ring. Alternatively, the 1-pyrrolyl derivative obtained from glutamic ester is directly cyclized by BBr3-promoted intramolecular acylation to the ester-substituted bicyclic pyrrole-cyclohexanone with retention of configuration. Third, catalytic hydrogenation of the bicyclic entities is entirely directed by the resident stereocenter to give the penultimate indolizidine intermediate or final product in an enantiomerically pure state. In the former case, transformation of the ring-substituent or substituents delivers the finished indolizidine in a few steps. As an illustration of the power of the methodology, the syntheses of some rare alkaloids of exotic origin, namely, indolizidines 167B, 209D, 209B, piclavine, and monomorine, are presented. By way of comparison, some other synthetic strategies leading to the same alkaloids, except piclavine, are outlined.

In this review we describe the asymmetrization of readily available Cs-symmetric compounds by enzyme-catalyzed reactions to provide chiral building blocks for the effective enantioselective synthesis of certain indole and quinolizidine alkaloids. By the asymmetrization of 1,2-disubstituted cyclo cyclohex-4-enes a series of class I alkaloids, such as (-)-antirhine, (-)-akagerine, and (posative)-meroquinene, have been synthesized from the relevant chiral precursors. By employing the same chemo-enzymatic approach, asymmetrization of Cs-symmetric 3,5-disubstituted piperidines provides access to 15,20-dihydrocleavamine and its analogues, as well as to (posative)-tacamonine. The synthetic design and details of the various syntheses are presented. In addition, the scope and prospects of the symmetrization-asymmetrization strategy are discussed with special reference to the quinolizidine alkaloids.