Reserpine introduction

We will continue with alkaloids by discussing a personal favorite (gephyro-toxin) and a classical target (reserpine) (Introduction-4). As with all of the natural (and unnatural) product targets discussed in this book, numerous total syntheses of gephyrotoxin and reserpine have been reported. It is instructive to compare syntheses, and look for strategic differences and similarities, and this will be done here as well as throughout this book. 

In the post-World War II years, synthesis attained a different level of sophistication partly as a result of the confluence of five stimuli (1) the formulation of detailed electronic mechanisms for the fundamental organic reactions, (2) the introduction of conformational analysis of organic structures and transition states based on stereochemical principles, (3) the development of spectroscopic and other physical methods for structural analysis, (4) the use of chromatographic methods of analysis and separation, and (5) the discovery and application of new selective chemical reagents. As a result, the period 1945 to 1960 encompassed the synthesis of such complex molecules as vitamin A (O. Isler, 1949), cortisone (R. Woodward, R. Robinson, 1951), strychnine (R. Woodward, 1954), cedrol (G. Stork, 1955), morphine (M. Gates, 1956), reserpine (R. Woodward, 1956), penicillin V (J. Sheehan, 1957), colchicine (A. Eschenmoser, 1959), and chlorophyll (R. Woodward, 1960) (page 5). ... 

An ingenious new method for the preparation of Woodward s intermediate (97) by Pearlman70 constitutes another formal synthesis of reserpine. The essence of this new approach is an adaptation of the de Mayo reaction which allows the introduction of vicinal aldehyde and acetic ester functions on to a double-bond (Scheme 13). An internal [2tt + 27r] photocyclization of the diene (98) gave the tetracyclic cyclobutane derivative (99), which was converted into the ester (100) by standard procedures. Methanolysis of the acetate function with concomitant retro-aldol fission completed the introduction of the vicinal aldehyde and acetic ester functions obvious manipulation then gave the desired intermediate (97). 

Stored serotonin can be depleted by reserpine in much the same manner as this drug depletes catecholamines from vesicles in adrenergic nerves (see Chapter 6 Introduction to Autonomic Pharmacology). 

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