The Stereochemistry of Reserpine, Deserpidine and Related Alkaloids^1,2

Abstract

In view of the close relationship of deserpidine with 3-epi-a-yohimbine73'8 the former appeared to have an epialloyohimbane skeleton, whose D/E ring juncture was unambiguously cis, as suggested by Janot's conversion of sempervirine (Ha) to d,/-alloyohimbane (Ilia) by catalytic hydrogena-tion9 and corroborated by stereospecific syntheses of d,/-epialloyohimbane (Ilia) and its diastereomers.1011 However the configuration at C-3 was by no means as clear. The sempervirine reduc-tion9 unfortunately was of little diagnostic value on this point because of the uncertainty of the stereochemistry of catalytic hydrogenation in alkaline medium, and became less so when it was discovered that a large-scale reduction led not only to the alio compound but also to some d,lepialloyohimbane.ld Whereas the production of the alio derivative by hydrogenation of d,l-A3alloyohimbene in the last step of a total synthesis103 suggested a syn-cis configuration (IVa) for allo-

Reserpine: A Challenge for Total Synthesis of Natural Products

“…The same group also first proposed the correct formula for this alkaloid . The relative configuration of reserpine was provided via chemical means by Aldrich, Diassi, Dickel, Dylion, Hance, Huebner, Korzun, Kuehne, Liu, MacPhillamy, Robb, Roychaudhuri, Schlittler, St. André, van Tamelen, Weisenborn, Wenkert, and Wintersteiner and confirmed in the first brilliant total synthesis achieved by Woodward . The relative configuration of reserpine was also confirmed later by Karle via X-ray crystallographic analysis .…”

“…7 The relative configuration of reserpine was also confirmed later by Karle via X-ray crystallographic analysis. 8 The absolute stereochemistry of reserpine was proposed by Schlittler 9 and Diassi 10 by the use of Klyne's extension of Hudson's lactone rule to the molecular rotation difference between reserpic and reserpic lactone 6,11 and later confirmed by Ban 12 using a chemical method.…”

Conformational Analysis of Some Alkaloids

“…The complete stereochemistry of these compounds resulted from a series of investigations carried out by SCHLITTLER, VAN TAMELEN, W ENKERT, W INTERSTEINER and their colleagues (2). Both ofthese alkaloids were known to possess the thermodynamically unstable configuration at C(3) (IOI, I36, I37); and since deserpidine could be converted into lX-yohimbine (So) under conditions known to cause epimerisation at C (3)…”

“…Reserpine (53) is the rr-methoxy analogue of deserpidine, and its stereochemistry was established largely by employment of arguments analogous to those already described for deserpidine (2). Thus, in the reserpine series, compounds possessing the structures (57; R = OCRa) (S2, I02, I7S) and ( The configurational problem posed by C m ) of reserpine was resolved by consideration of the products formed by treatment of methyl reserpate tosylate (53; OTs instead of 0 .…”