Synthesis of Several Cleistrioside and Cleistetroside Natural Products via a Divergent De Novo Asymmetric Approach

Abstract

The de novo asymmetric syntheses of several partially acylated dodecanyl tri- and tetra-rhamnoside natural products (cleistriosides-5 & 6 and cleistetrosides-2 to 7) have been achieved (19 to 24 steps). The divergent route requires the use of three or less protecting groups. The asymmetry was derived via Noyori reduction of an acylfuran. The rhamno-stereochemistry was installed by a diastereoselective palladium-catalyzed glycosylation, ketone reduction and dihydroxylation.

Achmatowicz reaction and its application in the syntheses of bioactive molecules

“…These compounds displayed antimicrobial activity against several methicillin-resistant Staphylococcus aureus . 302 Mezzettiaside-2 ( 271 ) and congeners were synthesized as anticancer/antibiotic oligosaccharides. 88 Merremoside D 272 299 and carbohydrates including digitoxin ( 273 , anticancer properties), 303 vineomycinone B2 ( 274 ), 304 vineomycin B2 trisaccharide ( 276 ) 305 (antitumor and antibacterial activities), methymycin analogues such as 275 (antibiotic activity), 306 and landomycins A and E ( 277a,b , antitumor activity) 307 were also synthesized using these protocols.…”

Structure activity relationship study of mezzettiasides natural products and their four new disaccharide analogues for anticancer/antibacterial activity

“…Previously, we have found success with the de novo synthesis 3 and medicinal chemistry study of a related class of carbohydrate based natural products, the cleistriosides and cleistetrosides, 4 using a Pd-catalyzed glycosylation. 5 These studies demonstrated that both the cleistriosides and cleistetrosides possessed both antibacterial and anticancer activity across a range of cell lines (NCI panel of 60 cell lines).…”

Structure–Activity Relationship Study of the Cleistriosides and Cleistetrosides for Antibacterial/Anticancer Activity

“…In 2010, we reported a divergent de novo asymmetric synthesis of both cleistriosides ( 1 and 2 ) as well as the six cleistetrosides ( 3–8 ), thus confirming the structures of the remaining members. 6 …”

“…6 Key to the approach was the efficient synthesis of a common trisaccharide intermediate 17 (Scheme 2). In a three-step asymmetric protocol acylfuran was converted into pyranone glycosyl donor 12 , 10, 11 which in turn is converted to pyranone 13 via a Pd-catalyzed glycosylation (1:4/Pd 2 (dba) 3 •CHCl 3 to PPh 3 ).…”