Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine.

The 9-azabicyclo[3.3.1]nonane ring system is present in several insect- and plant-derived alkaloids. (-)-Adaline (1) and (+)-euphococcinine (2), found in secretions of Coccinelid beetles, and (+)-N-methyleuphococcinine (3), isolated from the Colorado blue spruce Picea pungens, are members of this alkaloid family. Their unique bicyclic system with a quaternary stereocenter, and the potent biological activity exerted by these homotropane alkaloids, make them attractive synthetic targets. This work aims briefly to review the chemical ecology of Adalia bipunctata and the recent methodologies to obtain adaline (1), euphococcinine (2), and N-methyleuphococcinine (3).

(1)H chemical shift differences of Prelog-Djerassi lactone derivatives: DFT and NMR conformational studies.

This work reports an experimental and theoretical study of the conformational preferences of several Prelog-Djerassi lactone derivatives, to elucidate the (1)H NMR chemical shift differences in the lactonic core that are associated with the relative stereochemistry of these derivatives. The boat-like conformation of explains the anomalous (1)H chemical shift between H-5a and H-5b, in which the two methyl groups (C-8 and C-9) face H-5b, leading to its higher shielding effect.

Aqueous Barbier allylation of aldehydes mediated by tin.

The aqueous tin-mediated Barbier reaction affords good to excellent yields and moderate syn diastereoselectivity under basic and acidic conditions. The high yields and stereoselectivity observed in the case of o-substituted aldehydes suggest a cyclic organotin intermediate or transition state in K2HPO4 solution. A practical and efficient aqueous tin allylation of methoxy- and hydroxybenzaldehydes can be carried out in HCl solution in 15 minutes to afford the corresponding homoallylic alcohols in high yields. Aliphatic aldehydes give moderate to excellent yields with reaction times ranging from 30 to 60 minutes. Under these conditions, crotylation gives exclusively the gamma-product and the syn isomer is formed preferentially. For 2-methoxybenzaldehyde, an equilibration of the isomers to a syn/anti ratio of 1:1 can be observed after several hours. Control experiments with radical sources or scavengers give no support for radical intermediates. NMR studies suggest a mechanism involving an organotin intermediate. The major organotin species formed depends on the reaction medium and the reaction time. The use of acidic solution reduces the reaction times, due to the acceleration of the formation of the allyltin(IV) species.