Scalable synthesis of a new dihydroxylated intermediate for tetrodotoxin and its analogues

Article abstract of DOI:10.1055/s-0029-1218747

The synthesis of a novel intermediate for tetrodotoxin and its analogues, possessing two hydroxy groups at C-8 and C-11, is described. The procedure involves a Diels-Alder reaction between bromolevoglucosenone and a tert-butyldiphenylsilyl-protected isoprenol during which the C-11 group hydroxy is installed. Subsequent transformations, including an Overman rearrangement, affords a cyclohexene intermediate containing a trichloroacetamide moiety as a requisite amino functionality for installation of the guanidine unit present in tetrodotoxin. Hydroxylation at C-8 is carried out via neighboring group participation of the trichloroacetamide to furnish the desired diol intermediate. Georg Thieme Verlag Stuttgart.