Although the gigantic task of bringing the final stages in the total synthesis of vitamin B12 to the highest standard of excellence is now virtually completed, it remains to elucidate the intricate and not yet fully understood relationships among the various forms in which cobyric acid (factor V1a) occurs, and to prepare a reference sample of vitamin B12 itself in whose preparation no relays of any kind have been utilized. We hope to develop methods which will be generally applicable in the synthesis of macrolides, including the prototypes of the major subclasses within the group, partly in the hope that the presently obscure relationships between chemical structure and physiological activity in this important group might be elucidated. Consequently, during the coming year we shall prosecute these--and very possibly entirely different--approaches with increasing vigor.