Efficient, stereoselective synthesis of oxazolo[3,2-a]pyrazin-5-ones: novel bicyclic lactam scaffolds from the bicyclocondensation of 3-aza-1,5-ketoacids and amino alcohols.
[reaction: see text] The bicyclocondensation of 3-aza-1,5-ketoacids and amino alcohols furnished novel oxazolo[3,2-a]pyrazin-5-one scaffolds possessing angular, ring junction substituents in high yield with excellent levels of substrate-based diastereocontrol. Mild oxidation of serinol-derived scaffolds provided access to a new class of constrained dipeptide surrogates. Deprotection of the endocyclic amine contained within these scaffolds allows for further diversification via N-functionalization.
Bencsik
Josef R
JR
Array BioPharma, 3200 Walnut Street, Boulder, Colorado 80301, USA.
Kercher
Timothy
T
O'Sullivan
Michael
M
Josey
John A
JA
D000605:Amino Alcohols / Q000737:chemistry*; D001372:Aza Compounds / Q000737:chemistry*; D003500:Cyclization; D007651:Keto Acids / Q000737:chemistry*; D007659:Ketones / Q000138:chemical synthesis*; D007769:Lactams / Q000737:chemistry*; D010080:Oxazoles / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D011412:Propanolamines; D011409:Propylene Glycols / Q000737:chemistry; D011719:Pyrazines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000605:Amino Alcohols; D001372:Aza Compounds; D007651:Keto Acids; D007659:Ketones; D007769:Lactams; D010080:Oxazoles; D011412:Propanolamines; D011409:Propylene Glycols; D011719:Pyrazines; C072422:serinol