Pergamon Tetrahedron Letters, Vol. 37, No. 39, pp. 7043-7046, 1996 Copyright © 1996 Published by Elsevier Science Ltd Printed in Great Britain. All rights reserved 0040-4039196 $15.00 + 0.00 PII: S0040-4039(96)01592-4 Assignment of Absolute Configuration of the c~,~3-Unsaturated T-Methyl-T-Lactone of the Annonaceous Acetogenins by a Simple Enzymatic Method I P. Duret a, A.-I. Waechter a, B. Figad~rea, R. Hocquemiller a, A. Cav~ a*, C. Pi~rard b, and M. P~r~s b. aLaboratoire de Pharmacognosie, associ( au CNRS, Facult( de Pharmacie, Universit~ Paris-Sud, 92296 Chdtenay-Malabry, France. bLaboramire de RMN, Dept. de Neurophysiologie a~rospatiale, lnstitut de M~decine A(rospatiale B.P. 73, 91223 Br~tigny sur Orge, France. Abstract: The absolute configuration of the C-36 or C-34 chiral centers of Annonaceous acetogenins has been determined by simple enzymatic method focusing on the HPLC detection of NADH issued from the enzymatic oxidation of L- or D-lactic acid (obtained by oxidative cleavage of the terminal cc,[3- unsaturated y-methyl-y-lactone) to pyruvic acid by lactate dehydrogenase. Copyright © 1996 Published by Elsevier Science Ltd Annonaceous acetogenins are polyketides recently discovered up to now only from the tropical and subtropical plants of the Annonaceae family. They are characterized by a long alkyl chain of 35-37 carbon atoms possessing one or two tetrahydrofuran rings, several oxygenated functions (hydroxyl, ketone, acetoxyl) and a terminal y-methyl-T-lactone (Figure 1). In addition to these natural biologically active products, some natural precursors have been isolated which bear only the terminal T-lactone and either hydroxyl groups and/or 1,2-epoxides with double bonds on the alkyl chain. Most of these compounds exhibit interesting parasiticide, insecticide, immunomodulating properties and cytotoxic activities with promising antitumoral potential.2'3 Io"~ RI HO R 2 R~ "~4/32 73135~ (CH 2)[r~ ~ cn 3 ° /ViT\ .,.:" .... 1 H 3 C ~ / ~ OH 2 Uvaricin3 : 8 threo/trans/threo/trans/erythro H OAc H H Squamocin4: 8 threo/trans/threo/trans/erythro H OH OH H Motrilin 5 : 8 threo/trans/threo/trans/erythro H OH H OH Desacetyluvaricin6: 8 threo/trans/threo/trans/erythro H OH H H Isodesacetyluvaricin 7 : 8 threo/trans/threo/tran.~/threo H OH H H Neannonin 8 : 6 threo/trans/threo/trans/threo H OH H H Rolliniastatin-I In: 8 threo/cis/threo/cis/erythro OH OH H H Rolliniastatin-2 11 : 8 threo/trans/threo/trans/erythro OH OH H H 10 37 O-~ RI ~ HO OH OH 014 Almunequin9 trans / threo threo/ trans/ erythro Fig. 1 7043