A general and concise stereodivergent chiral pool approach toward trans-(4S,5R)- and cis-(4R,5R)-5-alkyl-4-methyl-γ-butyrolactones: Syntheses of (+)-trans- and (+)-cis-whisky and cognac lactones from d-(+)-mannitol.

A straightforward synthesis of (+)-trans-(4S,5R)- and (+)-cis-(4R,5R)-whisky lactones starting from d-(+)-mannitol has been reported here in fewer number of efficient steps compared to existing literature processes involving d-mannitol as the chiral pool starting material. Chiron approach directly translated chirality of d-mannitol to one of the two chiral centers in these target molecules. Toward this end, stereoisomerically pure trans- and cis-iodomethyl-γ-lactones were formed in the penultimate step. These two acted as versatile advanced common intermediates as they were also converted to the (+)-trans-(4S,5R)- and (+)-cis-(4R,5R)-cognac lactones, respectively. To the best of our knowledge, till date no synthesis of cognac lactones starting from d-mannitol has been reported. All these lactones are identified as the key aroma components of aged alcoholic beverages.

Enantiodivergent syntheses of (+)- and (-)-1-(2,6-dimethylphenoxy)propan-2-ol: A way to access (+)- and (-)-mexiletine from D-(+)-mannitol.

Chiron approach was used to acquire optically pure (R)- and (S)-1-(2,6-dimethylphenoxy)propan-2-ol, immediate precursors of (S)- and (R)-mexiletines, respectively. Two different routes were followed from a D-mannitol-derived optically pure common precursor to get the enantiomeric alcohols separately. Comparison of their specific rotation values with the corresponding literature values as well as exact mirror-image relationship between their CD curves proved their high enantiopurity. These alcohols were then transformed to the corresponding amine-drugs in an efficient one-step process instead of two steps described in the literature.

Chiron approach from D-mannitol to access a diastereomer of the reported structure of an acetogenin, an amide alkaloid and a sex pheromone.

A short, simple and convenient chiron approach to (3R,4S,5R)-(-)-3,5-dihydroxy-4-decanolide, a hitherto unknown diastereomer of the reported structure of a naturally occurring acetogenin, (+)-polyporolide has been accomplished starting from a commercially available, inexpensive chiral pool molecule D-(+)-mannitol in nine efficient steps. An advanced intermediate synthesized from D-(+)-mannitol in six steps toward this end was further employed successfully to access two different natural products bearing two contiguous stereogenic centers. As a result, first chiron approach to formal total synthesis of an amide alkaloid, (4R,5R,2E)-4,5-dihydroxy-1-(piperidin-1-yl)dec-2-en-1-one and total synthesis of a male sex pheromone in parasitic Hymenoptera, (4R,5R)-(-)-5-hydroxy-4-decanolide have also been achieved.