Dendritic aliphatic polyethers as high-loading soluble supports for carbonyl compounds and parallel membrane separation techniques

This paper describes the use of dendritic polyglycerol as a new high-loading polymeric support. The soluble polyether skeleton allows the parallel synthesis of small libraries on a large scale (1-5 mmol). Purification of polymer-bound products is easily achieved by a parallel dialysis apparatus, which was developed to separate up to 12 reaction mixtures simultaneously. The terminal 1,2-diol groups of polyglycerol (loading capacity: 4.1 mmol diol/g) can be directly coupled with carbonyl compounds without additional linker groups. At the same time the polyglycerol support acts as a polymeric ketal protecting group. The coupling of the carbonyl compounds occurs in high yields, and effective loading capacities of up to 3.5 mmol of ketone/g can be reached. The obtained polymeric acetals can easily be characterized by standard analytical techniques, such as NMR, IR, UV, and SEC. The versatility of this new polymeric support for solution-phase organic synthesis is demonstrated by two efficient polymer-supported syntheses: nucleophilic substitutions of gamma-chloroketones with amines and Suzuki-coupling on p-bromobenzaldehyde. The acid-catalyzed acetal cleavage with a solid-phase acidic ion-exchange resin in methanol demonstrates the orthogonal use of these soluble polymeric supports with conventional solid-phase reagents. Cleavage of products occurs in high yields, and almost complete recovery (>95%) of the polyglycerol support has been demonstrated after phase separation or ultrafiltration.     

A convenient synthesis of C-22 and C-25 stereoisomers of cephalostatin north 1 side chain from spirostan sapogenins

A simple transformation of the eight-carbon side chain of a natural spirostan sapogenin into the cephalostatin north 1 spiroketal moiety is described. This methodology, based on an intramolecular hydrogen abstraction reaction promoted by alkoxy radicals, permits the synthesis of C-22 and C-25 stereoisomers of the dioxaspiro[4.4]nonane cephalostatin ring system. The acid-catalyzed isomerization of the spirocenter in the different isomers is studied. [reaction: see text]     

Ammonium chloride-promoted four-component synthesis of pyrrolo[3,4-b]pyridin-5-one

A novel multicomponent synthesis of 5-aminooxazole starting from simple and readily available inputs is described. Thus, simply heating a methanol solution of an aldehyde 3, an amine 4, and an alpha-isocyanoacetamide 5 provided the 5-aminooxazole (1) in good to excellent yield. The reaction of 1 with alpha,beta-unsaturated acyl chloride 13 lead to the formation of pyrrolo[3,4-b]pyridin-5-one (2) in a single operation. A triple domino sequence, acylation/IMDA/retro-Michael cycloreversion, is involved in this new scaffold-generating reaction. After the observation that ammonium chloride can significantly accelerate the oxazole formation in toluene, a one-pot four-component synthesis of 2 is developed.     

Asymmetric total synthesis of dendrobatid alkaloid 251F

The dendrobatid alkaloid (-)-251F was synthesized. The key steps of the synthesis were (1) an asymmetric Diels-Alder reaction to establish four of the necessary stereocenters in the target, (2) a ring-opening/ring-closing metathesis reaction to establish a key [3.3.0] bicyclic intermediate, and (3) an intramolecular Schmidt reaction.