Isomer of biicarenone
(1) was synthesized. By comparing its ORD spectrum with that of the naturai product, the marine Q7 hydroquinone isolated as an inhibitor of mitotic ceiI division was shown to be (l'S,2'S)-1.
In 1980 Fenicai and his co-workers isolated biicarenone, an inhibitor of mitotic ceii division, from the brown seaweed (8ffurcarfa 9aalapauensls) harvested in Galapagos Isiamb Its structure was proposed as 2 on the basis of chemical and spectroscopic studies, without assignment of the absolute contiguration.l Our synthesis of (+)-3, however, reveaied its which was aho solved by its X-ray CrystaUoSrapbic auaiy& (Fii 3). Tbc structures of tkc remaiuiug two aeetals, 4~ and 4d, were determiucd by their derivation from 4b and 42, respeetivcty, by equilibration under acidic condition. Tire pure acetal4a was then treated with 2~ HCI to give (lR$R)-3, wkick was redueed with LAH to give a diol (U&D?)-5 (Fit 4). Tritytation of (lR,2R)-7 was wried out in the same mamrer as for (rt)-7 to give the monotrityl ether (tR,2f?)-8 together with by-products. The free OH group of 8 was then protected as t-butyklimetbylsilyl (TBS.) et&r. The re+mkiog (lR,2R)-13 was treated with Na/NHS to remove tbt trityf proteetivc group, &&g (lR,2R)-14. Swem oxidation of 14 yielded au aldcbyde (lR;LR)-16. Beyond this step, we followed the procedure developed by us for the syutke& of ( *)-1,2 aed (l&2/9-5 was prepared from lb. Tire overati yield of (l&2@5 from 4a was 34% in nine steps. Synthw+ta of (l'f?,2'ff)-Btfuroarenone (1).
Accord&S to tire previously reported method for tire syntbesia of (zt)-1, we converted {IF@?)-5 to (l'R,2'ff)-1 as shown in Fii 5. Tbc anion derived from 6 and IDA was alkylated with 18' to give IQ. Selective removal of the EZE protective tgroup of 19 with HCI-CHC13 was folIowed by treatmeut witk 2% NaOH-Et30 to give a ketone 20. Tkis was reduced with NaBH4 to g&e 21, tire bydroxy group of which was protected by acylation with pivaloyl chloride to fumisk 22. Deprotcction of the silyl ether of 22 yielded 23, Swem oxidation of which gave ae aldcbyde 24. Addition of tire d&ion derived from ~metbyl-l-bum-~oi to 24 10) The atomic coordinates for this work are available on request from the Dire&or of the Cambridge Crystallographic Data