Pergamon Tetrahedron Letters 39 (1998) 8755-8758 TETRAHEDRON LETTERS The Synthesis of (+)-Pericosine B Timothy J. Donohoe,* Kevin Blades, Madeleine Helliwell, ~ and Michael J. Waring Department of Chemistry, The University of Manchester, Oxford Road, Manchester, M 13 9PL, U. K. Nicholas J. Newcombe Zeneca Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, U. K. Received 22 June 1998; revised 8 September 1998; accepted 18 September 1998 Abstract: The first synthesis of (+)-pericosine B is described: this takes seven steps and proceeds in 10% overall yield. The key step in our work is a hydrogen-bonding controlled contra-steric dihydroxylation reaction using osmium tetroxide and an amine promoter. The absolute stereochemistry of the natural product was deduced from the known absolute stereochemistry of our starting material and moreover, the relative and absolute stereochemistry of our synthetic material was determined unambiguously from an X-ray crystal structure of an advanced intermediate. © 1998 Elsevier Science Ltd. All rights reserved. We were drawn to a recent report of the isolation of pericosine B (Scheme 1) from a micro-organism (a strain of Periconia byssoides) drawn from the gastrointestinal tract of the sea hare Aplysia kurodai) The relative stereochemistry of pericosine B was deduced from NMR data and its absolute configuration assigned without definitive proof) We considered pericosine B to be a worthwhile target as it exhibited significant activity (EDs0 = 4 pg/ml) in the P388 lymphocytic leukaemia test system and, as it had not been the subject of a successful synthesis, our work would also aim to confirm unambiguously the stereochemistry of the natural product. COOMe ~ OMe HO~3 ~1~ ~OH OH ( +)-pericosine B X X X ~ OMe ........ ~OMe OR ~ O M e OH HO"" ~ "OH HO" ~1 ~ "OH OH OH A B Scheme 1 The disconnection that we chose to simplify the target involved the introduction of the hydroxyl groups at C-3,4 via a dihydroxylation reaction. One would normally expect this reaction to give a diol with the wrong stereochemistry (A, Scheme 1): several years ago, Kishi demonstrated that chiral allylic alcohols (both cyclic and acyclic) were oxidised with osmium tetroxide and that they formed the syn, anti triol selectively) However, we have recently described methodology for performing the (hydrogen-bonding) directed dihydroxylation of cyclic allylic alcohols using osmium tetroxide with either a mono -3 or bidentate 4 ligand. As this methodology should give access to the syn, syn triol (B, Scheme 1), we proposed to use it in our synthesis. 0040-4039/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved. PII: S0040-4039(98)01989-3