Five-membered ring analogues of shikimic acid.
Shikimate and other intermediates of the shikimate-chorismate pathway are densely functionalized structures that seem to offer limited options for skeletal modification. We designed and synthesized cyclopentylidenes 1 and 2, as well as cyclopentenes 3 and 4, as novel ring-contracted analogues of shikimic acid. Enzymatic studies showed that analogues 1-3 are indeed processed by shikimate kinase to give phosphates 1-P, 2-P, and 3-P as five-membered ring analogues of shikimate-3-phosphate. In particular, analogue 1 is converted by the enzyme at a rate only 3.5-fold slower than that of the native substrate, while analogue 3 binds to shikimate kinase with an apparent Km of 1.7 mM, compared to 0.14 mM for shikimate.
An
M
M
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Toochinda
T
T
Bartlett
P A
PA
D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D012765:Shikimic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D013057:Spectrum Analysis; D013379:Substrate Specificity
D012765:Shikimic Acid; D017853:Phosphotransferases (Alcohol Group Acceptor); C022642:shikimate kinase