Asymmetric total synthesis of sperabillins B and D via lithium amide conjugate addition.
Diastereoselective conjugate addition of homochiral lithium (R)-N-allyl-N-alpha-methylbenzylamide to methyl (2E,5E)-hepatadienoate, followed by protecting group manipulation and subsequent iodocyclocarbamation allows a concise route to the core fragment, methyl (3R,5R,6R)-3,6-diamino-5-hydroxyheptanoate, of sperabillins B and D. Differentiation between the C-3 and C-6 primary amino groups of this core amino acid was readily achieved by treatment with acetone, giving the 5,6-isopropylidene and C-3-imine protected diamine, with subsequent regioselective acylation of the C-6-nitrogen facilitating the total synthesis of sperabillin D in 10.8% overall yield, and the first asymmetric synthesis of sperabillin B in 5.8% overall yield.
Davies
Stephen G
SG
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, UK OX1 3TA. steve.davies@chemistry.ox.ac.uk
Haggitt
Jane R
JR
Ichihara
Osamu
O
Kelly
Richard J
RJ
Leech
Michael A
MA
Price Mortimer
Anne J
AJ
Roberts
Paul M
PM
Smith
Andrew D
AD
D000577:Amides / Q000737:chemistry*; D000578:Amidines / Q000138:chemical synthesis / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D008094:Lithium / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*
D000577:Amides; D000578:Amidines; D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; C073530:sperabillin B; C073532:sperabillin D; D008094:Lithium