Alkaloid biosynthesis. Part XV. Partial synthesis and isolation of vincoside and isovincoside: biosynthesis of the three major classes of indole alkaloids from vincoside

Abstract

Tryptamine acts as a precursor of the indole alkaloids in Vinca rosea. Secologanin (1) condenses with tryptamine to yield vincoside (2) and isovincoside (5). the absolute configuration of these products is determined and their chemistry is explored. It is demonstrated by single-and double-labelling experiments that vincoside is the precursor of representative indole alkaloids from the Corynanthe, Aspidosperma, and lboga families in Vinca rosea ; isovincoside is not involved in these biosyntheses. Vinca rosea plants are shown to contain vincoside, isovincoside, and N-acetylvincoside by a combination of radiochemical dilution analysis and direct isolation. [5-3H] -Loganin fed to Vinca rosea is incorporated efficiently into vincoside and isovincoside.The steps are discussed by which vincoside is converted into the three types of indole alkaloids and it is proved that the side-chain unsaturation of vincoside is essential for operation of the later biosynthetic stages. The main part of this work has been briefly r e p~r t e d .~,~ 4 A. R. Battersby, P w e and Appl.

Purification and Properties of Strictosidine Synthase, the Key Enzyme in Indole Alkaloid Formation

“…Recent work in this laboratory [3-51 has demonstrated that, unlike previous findings [20,21] it is not vincoside, with the 3-P(R) configuration, but rather its epimer 3-m(S)-strictosidine [22] that is the universal [7,8] biosynthetic precursor for the vast majority of monoterpenoid indole alkaloids. This result was made possible by using cell-free extracts of C. roseus cell suspension cultures which produced substantial amounts of indole alkaloids 193.…”

“…Numerous examples show that the synthesis of secondary metabolites in higher plants is under the same stringent enzymatic control as that for primary metabolites; therefore strictosidine synthase is responsible for the synthesis of the natural intermediate strictosidine only. On the basis of this and previous [3][4][5]7,8] results we are entitled now to assume that the previously reported natural occurrence of vincoside in Catharanthus roseus [20,27] is either an error or a chemical artefact during feeding or work-up. The alkaloidal glucoside strictosidine isolated and characterized by G. N. Smith [22] is indeed the key intermediate in monoterpene indole alkaloid biosynthesis, as he had already assumed in 1968.…”

The intermolecular Pictet-Spengler condensation with chiral carbonyl derivatives in the stereoselective syntheses of optically-active isoquinoline and indole alkaloids

“…In vivo, it results from the Pictet-Spengler condensation of secologanin (154) and tryptamine (5) by plant species, in the presence of the enzyme strictosidine synthase, 128 or under biomimetic conditions in aqueous solution at pH= 4.5 (Scheme 29). 129 In the presence of the enzyme, the new chiral center is formed with complete stereoselectivity, while a 1:1 diastereomeric ratio is obtained in the absence of the enzyme. For many years, there was much controversy about the configuration of the new center of chirality at C-3, as well as about the question of which stereoisomer is the precursor of the alkaloids mentioned above.…”

The cDNA clone for strictosidine synthase from Rauvolfia serpentina DNA sequence determination and expression in Escherichia coli

“…INTRODUCTION The alkaloidal glucoside, strictosidine, was recognized in 1968 as a biosynthetic precursor of monoterpenoid indole alkaloids [I]. There was, however, much confusion about the stereochemistry of this first intermediate in the pathway [2,3] which was only clarified after the enzyme responsible for the stereospecific condensation of tryptamine with secologanin was discovered [4,5] and characterized [6,7]. This precursor of over 1800 indole alkaloids, some of high commercial value [8], has been unequivocally shown to possess a ICY configuration 191.…”