Total synthesis of a protected form of sphingofungin E using the [3,3]-sigmatropic rearrangement of an allylic thiocyanate as the key reaction.
An approach to the stereocontrolled synthesis of the protected form of sphingofungin E (32) starting from the known protected d-glucose derivative 3 is described herein. For the construction of a tetrasubstituted carbon atom that is substituted with nitrogen, the [3,3]-sigmatropic rearrangement of thiocyanate 8 was employed. Subsequent functional group interconversions afforded the highly functionalized fragment, allylic bromide 26. Its coupling reaction with the known C(12) hydrophobic segment 2, followed by further manipulation, completed the total synthesis.
Chirality extension of an oxazine building block en route to total syntheses of (+)-hyacinthacine A2 and sphingofungin B.
Concise and stereocontrolled syntheses of (+)-hyacinthacine A2 and sphingofungin B were achieved via a diastereomerically enriched oxazine intermediate. The key strategies include palladium(0)-catalyzed intramolecular oxazine formation and diastereoselective nucleophilic addition to an aldehyde. (+)-Hyacinthacine A2 was synthesized in 13 steps and 10.2% overall yield and the synthesis of sphingofungin B proceeded in a linear sequence over 15 steps and 6.9% overall yield from (R)-methyl 2-benzamido-3-((tert-butyldimethylsilyl)oxy)propanoate.
Diastereoselective Synthesis of 1,2-Diamines by Palladium Catalyzed Aza-Claisen Rearrangement
In the thermal rearrangement of allylic trichloroacetimidates 6, no 1,2-asymmetric induction can be observed. Palladium(II) catalyzed, however, the rearrangement takes place at 25 o C and yields diastereoselectively (de≥98%) the anti-1,2-diamines 7. The allylic trichloroacetimidates 6 can easily be prepared starting from α-amino acids