Application of intramolecular enyne metathesis to the synthesis of aza[4.2.1]bicyclics: enantiospecific total synthesis of (+)-anatoxin-a.
A concise synthesis of the potent nAChR agonist (+)-anatoxin-a (1) has been completed in a series of only nine chemical operations and 27% overall yield from commercially available D-methyl pyroglutamate (4). The synthesis features a novel procedure for the diastereoselective preparation of cis-2,5-disubstituted pyrrolidines leading to 10, which underwent an intramolecular enyne metathesis to afford a bridged azabicyclic intermediate that was transformed into 1. [reaction: see text]
Brenneman
Jehrod B
JB
Department of Chemistry and Biochemistry, The University of Texas, Austin, TX 78712, USA.
Martin
Stephen F
SF
D000480:Alkynes / Q000737:chemistry*; D001372:Aza Compounds / Q000138:chemical synthesis*; D001427:Bacterial Toxins / Q000138:chemical synthesis* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000494:pharmacology; D052998:Microcystins; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D011759:Pyrrolidines / Q000737:chemistry; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry; D013237:Stereoisomerism; D014326:Tropanes
D000480:Alkynes; D001372:Aza Compounds; D001427:Bacterial Toxins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D018722:Nicotinic Agonists; D011759:Pyrrolidines; D014326:Tropanes; C509783:anatoxin a; D011761:Pyrrolidonecarboxylic Acid