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Total Synthesis of 6-Amino-2,6-dideoxy-α-Kdo from d-Mannose
Oscar Javier Gamboa Marin1, Nazar Hussain1, Gokulakrishnan Ravicoularamin1
1Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique (INRS), 531, boul. des Prairies, Laval, Québec, Canada H7V 1B7.
Abstract:
3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) biosynthetic pathway is a promising target in antibacterial drug discovery. Herein, we report the total synthesis of 6-amino-2,6-dideoxy-α-Kdo in 15 steps from d-mannose as a potential inhibitor of Kdo-processing enzymes. Key steps of the synthetic sequence involve a Horner-Wadsworth-Emmons reaction for the two-carbon chain homologation followed by either a 6-exo-trig Pd-catalyzed reductive cyclization or a tandem Staudinger/aza-Wittig reaction with concomitant α-iminoester reduction, enabling the α-stereoselective formation of the Kdo-like six-membered azacyclic ring.
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