Synthesis of the alkaloid tyroscherin by an aldol/Curtius strategy

The alkaloid tyroscherin (2), which contains a vicinal anti-amino alcohol subunit was prepared from 4-hydroxyphenylpropionic acid (5) and meso-diol 9. After desymmetrization of diol 9 and suitable protecting group manipulations, one terminus was extended via a Claisen rearrangement giving rise to enoate ent-15. The missing carbon on the other end could be incorporated using MeMgCl/CuBr·SMe2 leading eventually to aldehyde ent-22. The acylated oxazolidinone 32 derived from acid 5 and aldehyde ent-22 were combined in an aldol reaction. A subsequent Curtius rearrangement on the carboxylic group furnished the amino function of tyroscherin (2). In a proof of concept study the same strategy was used to prepare tyroscherin analog 28.