ASYMMETRIC ALLYLBORATION OF 2-N,3-O-ISOPROPYLIDENE-N-BOC-L-SERINAL - DIASTEREOSELECTIVE SYNTHESIS OF THE CALICHEAMICIN GAMMA(I)(1) AMINO SUGAR

Syntheses of the calicheamicin amino sugar 6 and its erythro diastereo mer 7 have been completed by a sequence involving the asymmetric allyl boration of N-Boc-serinal acetonide L-8 with the tartrate ester modifi ed allylboronates (R,R)-9 and (S,S)-9, respectively. The reaction of(R ,R)-9 and L-8 in toluene provides 14 with 89:11 selectivity, whereas t he reaction of(S,S)-9 with L-8 in Et(2)O provides the diastereomer 15 with 90:10 selectivity. It is shown that the relatively modest diaster eoselectivity of these double asymmetric reactions is compromised by t he low enantiomeric purity of 8 (86-87% ee), and data are provided ind icating that these reactions should be highly diastereoselective (grea ter than or equal to 95:5 in each case) if performed with enantiomeric ally pure aldehyde. The two diastereomeric homoallylic alcohols, 14 an d 15, are easily elaborated into the targeted amino sugars 6 and 7 via the acetamide-substituted pyranosides 22 and 26. Methyl pyranosides 2 2a and 22e were shown to adopt preferentially the unexpected conformat ions B and D, with axial acetamide substituents, in nonpolar solvents, while the expected conformations A and C were strongly favored in d(6 )-DMSO because of hydrogen bonding interactions with the solvent. The syntheses of 6 and 7 reported herein are expected to facilitate the de sign and synthesis of analogs of the calicheamicin aryl tetrasaccharid e 3, which should prove useful in further analysis and applications of oligosaccharides as DNA binders.