Tetillapyrone and Nortetillapyrone, Two Unusual Hydroxypyran-2-ones from the Marine Sponge Tetilla japonica Rawiwan Watanadilok, † Pichai Sonchaeng, † Anake Kijjoa, ‡,§ Ana Margarida Damas, ‡,⊥ Luis Gales, ‡,⊥ Artur M. S. Silva, | and Werner Herz* ,∇ Bangsaen Institute of Marine Science, Burapha University, Bangsaen, Chonburi 20131, Thailand, Instituto de Cie ˆ ncias Biome ´ dicas de Abel Salazar, Universidade do Porto, 4099-003 Porto, Portugal, Centro de Estudos de Quı ´mica Orga ˆ nica, Fitoquı ´mica e Farmacologia da Universidade do Porto, Rua Anı ´bal Cunha, 4050-017 Porto, Portugal, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre, Porto, Portugal, Departamento de Quı ´mica Universidade de Aveiro, 3810 Aveiro, Portugal, and Department of Chemistry, The Florida State University, Tallahassee, Florida 32306-4390 Received February 9, 2001 Extraction of the marine sponge Tetilla japonica from the Bay of Thailand furnished tetillapyrone and nortetillapyrone, two unusual tetrahydrofurylhydroxypyran-2-ones, whose structures were established by NMR spectrometry and an X-ray analysis of tetillapyrone. There is little chemical information on sponges of the family Tetillidae, order Spirophorida, class Demospongia. Previous workers have described lipids from Cynachyrella alloclada, 1,2 and 3-O-methylsecosteroids have been iso- lated from Jereicopsis graphidiaphora, 3 while Fusetani and co-workers 4 reported isolation in very small amount of the potent cytotoxic macrolide cynachyrolide A from a marine sponge of the genus Cynachyra, which apparently is identical with spongistatin 4, one of a group of equally potent macrolides isolated from marine sponges of the genera Spongia, Spirastrella, and Hyrtios. 5 We have now studied a collection of Tetilla japonica Thiele from the Gulf of Thailand. In addition to 24-methylenecholest-5-en-3- ol, two unusual 5-tetrahydrofurylhydroxypyran-2-ones, 1a and 2, which we have named tetillapyrone and nortetil- lapyrone, were isolated. Results and Discussion Structure and stereochemistry of the left half common to both substances, a 2-substituted 4-hydroxy-5-hydroxy- methyltetrahydrofuran, were easily deduced from the 1 H and 13 C NMR spectral data listed in Tables 1 and 2. In both instances COSY and NOESY correlations established that a low-field proton (H-7), resonating near δ 6.17 and alpha to the oxygen of the tetrahydrofuran ring, was adjacent to a methylene group, trans to a proton (H-9) deshielded by a hydroxyl and cis to a proton (H-10) on carbon carrying a -CH 2 OH group. Formation of a di- acetate, 1b, whose 1 H and 13 C NMR spectra (Table 1) reflected the expected changes confirmed the assignments, although the unusual chemical shift (δ 6.17) of the proton at C-2 of the tetrahydrofuran ring demanded attention. On the other hand structure elucidation of the right halves of both molecules presented difficulties. In the case of 1a the 1 H NMR spectrum indicated the presence of a vinylic hydrogen at δ 7.69 (H-4 in the final formula, C-4 at δ 136.22), apparently at the -position of a conjugated ketone or lactone and allylically coupled to a vinyl methyl at δ 1.76. The latter was absent in the case of the nor- derivative and replaced by another vinylic hydrogen at δ 5.63. By HMBC the vinylic hydrogen of 1a at δ 7.69 was attached to a carbon atom two bonds removed from a second carbon represented by a singlet at δ 150.41, appar- ently also vinylic or aromatic and possibly attached to a third hydroxyl group whose signal appeared at δ 11.28. The third hydroxyl group was not affected by conversion of 1a to its diacetate and was not enolic, as shown by the absence of a positive FeCl 3 test and by the lack of change in the UV absorption on addition of base. The 10 carbons, 14 hydrogens, and four oxygenssthree belonging to the three hydroxyls and one to the tetrahy- drofuran ringsdeduced from the 1 H and 13 C NMR evidence presented in the previous paragraphs accounted for only 198 of the 242 mass units in the mass spectrum of tetillapyrone, leaving apparently one carbon and two oxygen atoms unaccounted for. Since the substance fur- nished suitable crystals, an X-ray analysis was therefore undertaken. The surprising result is displayed in Figure 1, which shows that the substance is a 5-tetrahydrofuryl- 6-hydroxypyran-2-one, 1a, which in the solid state is essentially ionic, i.e., in the form of an enolate. In the crystal there was no evidence for a hydrogen atom on O-2 * To whom correspondence should be addressed. Tel: 1-850-644-2774. Fax: 1-850-644-8281. E-mail: jdulin @chem.fsu.edu. † Burapha University. ‡ Instituto de Cie ˆncias Biome ´dicas. § Centro de Estudos de Quı ´mica Orga ˆ nica, Fitoquı ´mica e Farmacologia da Universidade do Porto. ⊥ Instituto de Biologia Molecular e Celular. | Departamento de Quı ´mica Universidade de Aveiro. ∇ Department of Chemistry, The Florida State University. 1056 J. Nat. Prod. 2001, 64, 1056-1058 10.1021/np0100690 CCC: $20.00 © 2001 American Chemical Society and American Society of Pharmacognosy Published on Web 08/03/2001