The anticancer agent rocaglamide contains a novel bicyclo[3.3.0]octanol structure. The approach to this molecule involved the preparation of a hydroxy ketone intermediate via a samarium-mediated cyclization. This ketone was then converted into an excellent Michael acceptor via novel chemistry. Subsequent steps led to the preparation of an isomer of rocaglamide. An X-ray determination supported our view that cuprate addition occurred with unusual concave selectivity.
77matographed on silica gel (water-saturated ethyl acetate) to yield the product, 0.36 g (31% yield): [ a I z 6~ -21.8' (c 0.40, H20); 'H NMR (200 MHz, D20) 6 1.03, 1.20 (9, 6 H, CH3), 1.37 (dd, J = 13 Hz, J = 11.8 Hz, 1 H, C5-H,), 1.83 (dd, J = 13 Hz, J = 4. To prepare D-fructose, the condition was essentially the same except that no aldehyde was used. Triosephosphate isomerase (500 units) was added to the mixture in addition to the aldolase.The product was identified with HPLC and compared with that of authentic D-fructose.Fuculose-1-phosphate Aldolase Catalyzed Reaction:Preparation of D-Ribulose. To a Tris buffer solution (85 mL, 10 mM, pH 7.5, containing 6 mM KC1, 6 mM CO(NO,)~) were added sodium arsenate (200 mmol), glycoaldehyde (1.7 g, 14.2 mmol), and dihydroxyacetone (3.2 g, 17.8 mmol). The solution was adjusted to pH 7.5 followed by adding 100 mg of the enzyme-containing E. coli cells and 1 mg of lysozyme (51 000 pm) to break the cells. The mixture was stirred for 24 h. TLC showed no glycoaldehyde was present, R, 0.75. The mixture was lyophilized and triturated with 4 X 75 mL of methanol and filtered, and the filtrate was evaporated. The product was purified on Dowex 50 (Ba2+) column with water as a mobile phase to give 1.70 g of product, which was identical with authentic D-ribulose (from Aldrich) by HPLC ( t R = 4.9 min) and NMR analyses. Rhamnulose-1-phosphate Aldolase Catalyzed Reactions.The E. coli cells containing this enzyme were used to prepared L-xylulose from DHA and glycoaldehyde under the same conditions as that for the preparation of D-ribulose. The product obtained (1.60 g, 76% yield based on glycoaldehyde) was identical with authentic L-xylulose (from Aldrich) by HPLC (tR = 5.0 min) and NMR analyses. When L-lactaldehyde (4.75 mmol, prepared by acid hydrolysis of the dimethyl acetal precursor)lB was used as acceptor and dihydroxyacetone (5.56 mmol) as donor, a mixture of L-rhamnulose and L-rhamnose (0.61 g, 71 % yield) was obtained based on 'H NMR, 13C NMR, and HPLC analyses ( t~ rhamnose = 5.2 min; tR rhamnulose = 4.8 min; the ratio of aldose to ketose is 0.6:0.4).Acknowledgment.