Stereoselective syntheses of the octahydropyrano[2,3-b]pyridine DE core of 'Upenamide via a stannous chloride-induced deacetalisation-cyclisation procedure

Two stereoselective syntheses of the octahydropyrano[2,3-b]pyridine DE hemiaminal core of the macrocyclic alkaloid 'upenamide are described. The syntheses proceeded through an efficient stannous chloride-induced deacetalisation-cyclisation procedure. The aza-annulation was stereoselective affording a single stereoisomer having the same relative configuration as in the natural product. The cis ring junction and the cis relationship between 2-H and 8a-H were established by NMR spectroscopy and confirmed by X-ray crystallography. An asymmetric synthesis of the octahydropyrano[2,3-b]pyridine ring system is also disclosed. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007).