The second generation synthesis of (±)-berkeleyamide D

Six-Step Total Synthesis of Azaspirene

“…Silyl ether 10 was transformed to enol derivative 12 through a hydroxy to methoxy substitution followed by an oxidation of the secondary alcohol group in 11 . Ketone 12 underwent a facile intramolecular epoxide opening in the presence of base to afford spirocycle 13 consistent with Kuramochi’s reports . Spirocycle 13 , upon hydrolysis under acidic conditions, yielded (±)-berkeleyamide D ( 2 ) in 10 steps from commercially available materials.…”

Strategies and methodologies for the construction of spiro-γ-lactams: an update

“…An improved methodology for the synthesis of the metalloproteinase-3 and caspase-1 inhibitor, (±)-berkeleyamide D (302) has been reported by Kuramochi and co-workers (Scheme 75). 106 The protocol involves the synthesis of ketal 301 via a Darzens reaction of isobutylglyoxal (299) and -bromo-β-ketoamide 300. Deprotection of 301 followed by intramolecular spirocyclization via epoxide ring opening triggered by the enol moiety led to the target compound in 23% yield over a two-step sequence and in 11% overall yield, a 4-fold improvement of the overall yield of the previous reported synthesis.…”

α-Halogenoacetamides: versatile and efficient tools for the synthesis of complex aza-heterocycles

“…This reaction is further favored by the presence of a ketone in βposition as in the beautiful domino Darzens reaction/hemiaminal formation described by Kuramochi and co-workers in their development of the synthesis of natural products (Scheme 27). [98][99][100] For that purpose, the authors engaged ketoaldehydes 71 with αbromo-β-ketoacetamides 1 in the presence of Et 3 N and were rewarded with the creation of 3 bonds during the domino sequence. Indeed, the Darzens reaction was followed by an intramolecular addition of the nitrogen atom to lead directly to the desired bicyclic product 72.…”