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Short, "one-pot" syntheses of malondialdehyde adducts of deoxyguanosine, deoxyadenosine, and deoxycytidine are described. These syntheses proceed in improved yield and easier purification than previous syntheses and are well suited for the preparation of isotopically labeled nucleoside adducts for biomarker and metabolic studies.

The BC ring system of upenamide was assembled using a stereoselective Diels-Alder reaction followed by a Staudinger/aza-Wittig/imine hydrolysis reaction. Stereoselective aldol coupling with an aldehyde that incorporates the DE ring system led to an advanced synthetic intermediate en route to the marine alkaloid upenamide.Upenamide, a unique macrocylic alkaloid was isolated from the crude extract of the marine sponge Echinochalina collected from Derawan Island in Indonesia, as reported by Scheuer in 2000. 1 Structurally, upenamide features an unsaturated 20-membered macrocycle interconnecting spirooxaquinolizidinone and hemiaminal ring systems; likely derived from a reduced bis-3-alkylpyridine macrocycle according to the biogenesis of related marine alkaloids such as the xestospongins, manzamines and saraines. 2 The structure of (−)-upenamide was elucidated primarily by a series of NMR experiments. While the absolute configuration of the spirooxaquinolizidinone substructure was assigned by NMR analysis of the S-and R-Mosher esters derived at the C11 hydroxyl group, 3 the absolute stereochemistry of the bicyclic hemiaminal ring system was left unassigned. Thus, the structural information currently available is in agreement with the 27R, 30S, 32S or 27S, 30R, 32R isomers (Figure 1). One approach to distinguishing between these two structures is by enantioselective total synthesis of upenamide and correlation with natural (−)-upenamide.In bioassays, upenamide did not show cell growth inhibition against P388, A549 and HT29 cancer cell lines. Further biological evaluation has not been reported perhaps due to insufficient quantities of upenamide. Since sponge collection from the Derawan island is now strongly restricted it is doubtful the current supply of upenamide will be increased by isolation, leaving total synthesis as the only viable material supplement. 4As a means of full stereochemical assignment of (−)-upenamide, our synthetic strategy required delivery of 27R, 30S, 32S upenamide and the mirror image of the corresponding 27S, 30R, 32R isomer (Figure 1) by stereoselective aldol coupling of racemic (±)-2 and (−)-3 followed by the eventual completion of the upenamide ring system (Scheme 1). This synthetic assembly, in principle, provides sufficient stereochemical information to unambiguously assign the structure of (−)-upenamide by spectral and optical properties comparison to natural material. Earlier we described a stereocontrolled synthesis of (−)-3. 4c Herein we describe a gary.a.sulikowski@vanderbilt.edu. The preparation of the spirocyclic ring system (±)-2 presents a significant synthetic challenge due to the required control of three contiguous stereocenters including a central quaternary carbon. 5 A logical precursor to (±)-2 is aldehyde 4 which we anticipated could be produced by a reductive cylization of azido lactone 5, a bicyclic ring system derived from a Diels-Alder reaction (Scheme 1). Feringa has investigated the Diels-Alder reaction of gammaalkoxybutenolides, however, only an intramolecu...

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