Ulapualides

Several nitrogen-containing macrolides were reported to be obtained from marine sources. Ulapualides A (254) and B (255), possessing unique structures with three contiguous oxazoles, were isolated from the egg... 

The compounds isolated from the nudibranch Hexabranchus sanguineus varied with collecting location but usually included dihydrohalichondra-mide (261) and tetrahydrohalichondramide (268). Compounds 261, 263, 265, and 268 show antifungal activity and inhibit cell division in the fertilized sea urchin egg assay (218). Three cytotoxic macrolides, mycalolides A-C (269-271), were isolated from a Japanese sponge of the genus My-cale, and their structures were elucidated to be hybrids of ulapualides and halichondramide (219). 

Roesner, J.A. and Scheuer, P.J., Ulapualide A and B extraordinary antitumor macrolides from nudi-branch eggmasses, J. Am. Chem. Soc., 108, 846, 1986. 

The eggs of the nudibranch Hexabranchus sanguineus collected off the coast of Hawaii have yielded the macrolides ulapualide A (62) and ulapaulide B (63) (25) both of which incorporate the unprecedented trisoxazole moiety. These compounds were obtained as colorless oils whose structure determination was... 

C-NMR data for some of the more complex and/or recently discovered alkaloids have been reported (Table III). The structure of the trisoxazole portion of ulapualide B (63) was elucidated largely by analysis of fully coupled and partially decoupled 13 C-NMR spectra. A series of simple oxazoles has been subjected to systematic analysis by 13 C-NMR spectroscopy and provides useful models (125). 

The structural diversity of molluscan chemistry can be seen in compounds 32-40 in Scheme 6.2 and includes a number that have been included in clinical studies such as the kahalalides and the dolastatins 34 and 37. An example of material exchange from prey to predator can be shown in kahalide F 32, which can be found in both the sea hare Elysia sp. and its diet of Bryopsis sp. algae. In addition, the structural similarity of ulapualide A 23 and that of the compounds mycalolide 21 and halichondramide 22 (Scheme 6.1 Part 3), found in a diverse array of sponges, indicates a possible alternate source for this structure class. 

In the late 1980s, ulapualide A 23 was isolated from the egg masses of the nudibranch Hexabranchus sanguineus120 and was shown to inhibit the growth of Candida albicans and L1210 leukaemia cell proliferation. A molecular mechanics study initially suggested that the relative stereochemistry was related to that of the halichondramides and mycalamides,350 however, the... 

A new synthesis of (-)-ulapualide A was completed by the group of Pattenden following a previous synthesis of a different diastereisomer whose chiroptical and H NMR spectroscopic data were identical with those of the natural product <07 AG(E)4359>. The first synthesis of siphonazole 119 was completed. Both the oxazole rings were constructed using rhodium carbene chemistry <07CC1508>. 

Chattopadhyay, S.K., and Pattenden, G., Towards a total synthesis of ulapualide A. A concise synthesis of the fm-oxazole macrolide core and entire carbon skeleton, Synlett, 1345, 1997. 

Fusetani, N., Yasumuro, K., Matsunaga, S., and Hashimoto, K. (1989). Mycalolides A-C, hybrid macrolides of ulapualides and halichondramide, from a sponge of the genus Mycale. Tetrahedron Lett. 30, 2809-2812. 

In the total synthesis of filipin III (141) [95], macrocyclization under K2CO3/ 18-crown-6 conditions proceeded (Fig. 4), although the cyclization was unsuccessful under LiCl/DBU conditions, which were useful for roflamycoin (140) [94] and roxaticin [93]. The total synthesis of ulapualide A (142) was accomplished via three Wittig-type couplings [101]. 

---