Synthesis and assignment of the absolute configuration of the anti-Helicobacter pylori agents CJ-12,954 and CJ-13,014.
The synthesis of the spiroacetal-containing anti-Helicobacter pylori agents (3S,2''S,5''S,7''S)- (ent-CJ-12,954) and (3S,2''S,5''R,7''S)- (ent-CJ-13,014) has been carried out based on the convergent union of a 1:1 mixture of heterocycle-activated spiroacetal sulfones and with (3S)-phthalide aldehyde . The synthesis of the (3R)-diastereomers (3R,2''S,5''S,7''S)- and (3R,2''S,5''R,7''S)- was also undertaken in a similar manner by union of (3R)-phthalide aldehyde with a 1:1 mixture of spiroacetal sulfones and . Comparison of the (1)H and (13)C NMR data, optical rotations and HPLC retention times of the synthetic compounds (3S,2''S,5''S,7''S)- and (3S,2''S,5''R,7''S)- and the (3R)-diastereomers (3R,2''S,5''S,7''S)- and (3R,2''S,5''R,7''S)-, with the naturally occurring compounds, established that the synthetic isomers and were in fact enantiomeric to the natural products CJ-12,954 and CJ-13,014. The (2S,8S)-stereochemistry in protected dihydroxyketone , the precursor to the mixture of spiroacetal sulfones and was established via union of readily available (S)-acetylene with aldehyde in which the (4S)-stereochemistry was established via asymmetric allylation. Deprotection and cyclization of protected dihydroxyketone afforded an inseparable 1:1 mixture of spiroacetal alcohols and that were converted into a 1:1 inseparable mixture of spiroacetal sulfones and . Phthalide-aldehyde was prepared via intramolecular acylation of bromocarbamate in which the (3S)-stereochemistry was established via asymmetric CBS reduction of ketone .
Brimble
Margaret A
MA
Department of Chemistry, University of Auckland, 23 Symonds St., Auckland, New Zealand. m.brimble@auckland.ac.nz
Bryant
Christina J
CJ
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D016480:Helicobacter pylori / Q000187:drug effects; D008968:Molecular Conformation; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity
D000900:Anti-Bacterial Agents; D001572:Benzofurans; C109706:CJ 12954; C109705:CJ 13014; D013141:Spiro Compounds