Xestoquinol

The yellow pigment halenaquinol sulfate (410) has been isolated from the Okinawan sponge Xestospongia sapra and is a pentacyclic hydroquinone [345]. The absolute stereochemistry was determined to be 6S by comparing the CD spectrum of a derivative with a theoretically calculated spectrum [346]. Theoretical calculation of CD spectra of halenaquinol sulfate (410) isolated from X. exigua and X. sapra determined that the absolute stereostructure was 12bS [347]. The pentacyclic compound, xestoquinol sulfate (411) has been isolated from an Okinawan collection of X. sapra and its structure was elucidated on the basis of spectroscopic data and a chemical conversion [348]. 

We achieved the first total synthesis of (+)-halenaquinol 2 and (+)-halenaqui-none 1, by which the absolute configurations of (+)-l and (+)-2 theoretically determined were experimentally proved to be correct. On the other hand, the absolute stereochemistry of xestoquinone has remained undetermined. Next, we carried out the first total synthesis of xestoquinone (+)-4 and xestoquinol 62 although the latter compound has never been isolated as a natural product.20... 

The hydroquinone dimethyl ether moiety of (+)-74 was oxidatively cleaved with ammonium cerium(IV) nitrate ((NH4)2Ce(N03)6), yielding xestoquinone (12b5)-(+)-4 as crystals mp 213-216°C dec natural, mp 212-214°C dec (Scheme 15). Xestoquinone (12bS)-(+)-4 was finally reduced with sodium hydrosulfite to afford xestoquinol (12bS)-62 in an almost quantitative yield. Although xestoquinol 62 has not been isolated yet as a natural product, the spectroscopic data of the synthetic sample reasonably support its structure. The first total synthesis of (+)-xestoquinone and xestoquinol has been thus achieved. 

Figure 14. CD and UV spectra of xestoquinol naphthalene-diene derivative (4, 12bS)-75 in CH3CN.20...

The absolute stereostructures of halenaquinone (+)-l, halenaquinol (+)-2, halenaquinol sulfate (-i-)-3, xestoquinone (+)-4, and xestoquinol 62, novel pentacyclic marine natural products isolated from tropical marine sponges, were theoretically determined to be 12bS, respectively, on the basis of the calculation of the CD spectra of naphthalene-diene derivatives by the re-electron SCF-CI-DV MO method. These studies also clarified that the theoretical CD method was applicable to such complex natural products. 

We have succeeded in the first total synthesis of (+)-halenaquinone 1, and (+)-halenaquinol 2, (+)-xestoquinone 4, and xestoquinol 62 by starting from the (8a/ )-(-)-Wieland-Miescher ketone 33 and also have experimentally determined their absolute configurations to be 12b5. The conclusions on the absolute configuration are in agreement with those derived from the theoretical calculation of CD spectrum. So, these first total syntheses of (+)-halenaquinol, (+)-halena-... 

In addition to these examples, it is worth mentioning alisiaquinones and alisiaquinol, two other pentacyclic derivatives that are structurally related to halenaquinones and xestoquinols, but are isolated from an rmdetermined deep-water sponge collected from the Norfolk Rise, New Caledonia. These compounds showed antimalarial activity (Desoubzdanne et al., 2008). 

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