The Art of Innovation in Organic Chemistry:  Synthetic Efforts toward the Phomoidrides

Total Synthesis of (±)‐Phomoidride D

“…Since the isolation and structural elucidation of the two fungal secondary metabolites, phomoidride A ( 1 ; CP‐225,917) and phomoidride B ( 2 ; CP‐263, 114; Figure ), by researchers at Pfizer, numerous groups have devoted efforts toward developing new synthetic strategies to construct these natural products . While the cholesterol‐lowering and anticancer properties displayed by 1 and 2 certainly motivated synthetic efforts, there is little doubt that the unique and complex architecture inherent to the phomoidrides has served as the primary inspiration to what has proven to be a variety of markedly creative approaches, and four completed total syntheses . Studies toward these targets also led to the discovery of two other congeners, phomoidride C and phomoidride D ( 3 and 4 , respectively, Figure ), which differ in the relative stereochemistry at C7.…”

Total Synthesis of (±)‐Phomoidride D

“…Since the isolation and structural elucidation of the two fungal secondary metabolites,p homoidride A( 1;C P-225,917) and phomoidride B( 2;C P-263, 114;F igure 1), by researchers at Pfizer, [1] numerous groups have devoted efforts toward developing new synthetic strategies to construct these natural products. [2] While the cholesterol-lowering and anticancer properties displayed by 1 and 2 certainly motivated synthetic efforts,t here is little doubt that the unique and complex architecture inherent to the phomoidrides has served as the primary inspiration to what has proven to be avariety of markedly creative approaches, [2,3] and four completed total syntheses. [4] Studies toward these targets also led to the discovery of two other congeners,p homoidride Ca nd phomoidride D( 3 and 4,r espectively,F igure 1), [4f, 5] which differ in the relative stereochemistry at C7.…”

Synergistic Catalysis: Metal/Proton‐Catalyzed Cyclization of Alkynones Toward Bicyclo[3.n.1]alkanones

“…[6] Owing to the promising biological properties and challenging structures of these bicyclic molecules,c onsiderable research efforts have been devoted to develop efficient methods to construct these carbon-bridged medium-sized rings. [2,8] Tr aditionally,t he bicyclo[3.n.1] systems were constructed through radical cyclization [Scheme 2, Eq. (1)] [9] or cationic cyclization [Eq.…”

“…2) were then investigated (entries [8][9][10][11][12][13]. When TsOH and CF 3 COOH were added into the reaction system, at race amount of the desired bicyclo[3.2.1]alkanone product 2a could be observed (entries [8][9]. Encouraged by this observation, as tronger Brønsted acid, TfOH, was then employed as the co-catalyst.…”