A diastereodivergent strategy for the asymmetric syntheses of (-)-martinellic acid and (-)-4-epi-martinellic acid
Davies SG., Fletcher AM., Lee JA., Lorkin TJA., Roberts PM., Thomson JE.
Asymmetric syntheses of (-)-martinellic acid and (-)-4-epi-martinellic acid were achieved in 20 steps from commercially available starting materials using a diastereodivergent strategy. The conjugate addition of lithium (R)-N-allyl-N-(α-methyl-p-methoxybenzyl)amide to tert-butyl (E)-3-[2′-(N,N-diallylamino)-5′-bromophenyl]propenoate and alkylation of the resultant β-amino ester with methyl bromoacetate were used as the key steps to install the C(9b) and C(3a) stereogenic centres, respectively. Subsequent cyclisation to the corresponding pyrroloquinolin-2-one and reduction of the C(4)-carbonyl group was followed by two complementary procedures for olefination and concomitant intramolecular Michael addition, which gave both C(4)-epimers of this tricyclic molecular architecture in >99:1 dr. Subsequent elaboration of these templates provided access to (-)-martinellic acid and, for the first time, (-)-4-epi-martinellic acid. © 2013 Elsevier Ltd. All rights reserved.