The project proposed herein is a methodology and synthetic investigation of the natural product cyclodidemniserinol trisulfate, a sulfated serinolipid that inhibits HIV-1 integrase. The specific aims of the study are: 1) the use of a rhodium(II)-catalyzed tandem cyclization- cycloaddition reaction of an a-diazo carbonyl compound to generate stereoselectively the 6,8 dioxabicyclo[3.2.1]octane-ring system of cyclodidemniserinol trisulfate, 2) study the effects of pre-existing stereochemistry in the a-diazo carbonyl compound and the stereocenters influence on the facial selectivity in the 1,3-dipolar cycloaddition, 3) determine the absolute stereochemistry of the natural product, 4) and synthesize various diastereomer analogs. The synthesis of cyclodidemniserinol trisulfate and analogs will be beneficial to the study of the mechanism of action on HIV integrase and possibly lead to the discovery of new more potent HIV-1 integrase inhibitors.