NEWS AND VIEWS ORGANIC CHEMISTRY------Highlights include the use of organo-iron New routes to natural products chemistry to produce not only the key spiroacetal (A in figure) but also the John Mann oleandrose subunits (C); and the coupling of the fragments A and B to form the AT one time, the synthesis of complex spectrum of activity against animal aglycone. The final steps of the synthesis molecules was the noblest pursuit for an parasites. The compounds seem to act at were achieved with the minimum of organic chemist. During the past ten GABA receptors and to maintain the protection/deprotection of hydroxyl years, however, many organic chemists chloride channels in the open form, thus groups by an elegant exploitation of the have been lured by the fat research grants potentiating the inhibitory activity of selective reactivities of these groups. The and contemporary glamour of bio-organic GABA at neuronal junctions. Several overall route is flexible enough to allow chemistry. So it is good to see two excel­ avermectins are now produced routinely for the synthesis of analogues, and should lent examples of natural-product synthesis using fermentation technology, reported by Ley et al. ,_,. The biological and ivermectin (the dihydro­ OPIOIIOHI2• interest of one of the compounds (myo­ analogue of avermectin B1a) is OH IHOI2101PO;o:-OH inositol I ,4,5-triphosphate (IP,)) is well at present sold in more than 60 OH-- ; OH known, but that of the other (the anti­ o: HO countries worldwide for the OPIOIIOHI2 parasitic agent avermectin Bla), is control of both internal and o- myo -inositol- also considerable. external parasites of livestock. 1,4,5-trisphosphate There has been enormous interest in the Notwithstanding this availabi­ inositol phosphates, in particular the role lity, the compounds are challen­ Ho .•• A. TBOMSO.,,~O,, ••. )-_0) 'OH .·•'' ··o '·H of IP, as a second messenger, ever since ging targets for synthesis. I c 0 OTBOt.AS their involvement in intracellular signal­ Avermectin B1a, for example, ling was first proposed by Mitchell' in has 20 stereocentres and a host ~A 1975. A number of syntheses of both the of delicate functional groups; natural compounds and certain analogues and to probe the biological have been described, but almost all of activity of these interesting these commence with myo-inositol and molecules, selected analogues SO~h proceed via a tortuous sequence of must be prepared. Several re- 0 ....._ •o ~enantiomers Leg 127 and Leg 128 shipboard scientific parties (both natural and unnatural) with only minor modifications. The approach LEGS 127 and 128 of the Ocean Drilling geology and geophysical structure of the makes a novel range of IP,-related com­ Program spent the summer and early Japanese Islands point to the presence of pounds readily accessible for biological autumn of 1989 drilling at six sites in the continental crust beneath the Japan arc, investigation. Japan Sea (see figure). The goals of these which in turn calls for a history involving The avermectins are mould metabolites two expeditions aboard the RV JOIDES continental rifting and separation of the first isolated in 1976 from a strain of Resolution were to assess the timing, style arc from mainland Asia through back-arc 9 Steptomyces avermitilis • They were and dynamics of the opening of this sea formation of the Japar: Sea - a tectonic shown to have high potency and broad and to decipher its subsequent palae­ scenario thought to be responsible for the oceanographic evolution. evolution of many ancient continental The western Pacific region is character­ margins. 1. Ley, S.V., Sternfeld, F. Tetrahedron Lett. 29, 5305-5308 Sixteen years ago, Leg 31 of the Deep (1988). ized by a series of marginal basins bor­ 2. Ley, S.V., Parra, M., Redgrave, A.J., Sternfeld, F. &Vidal, dered by many island arcs. The formation Sea Drilling Project (DSDP) attempted A. Tetrahedron Lett. 30, 3557-3560 (1989). of these marginal seas is intimately linked to study the history of the Japan Sea but 3. Ley, S.V., Parra, M., Redgrave, A.J. & Sternfeld, F. Tetra· hedron 46, 4995-5026 (1990). to the subduction of oceanic crust at adja­ failed to penetrate the sedimentary cover 4. Armstrong, A. & Ley, S.V. Synlett 323-325 (1990). cent deep-sea trenches. This process fuels and sample basement rocks, thus leaving 5. Diez-Martin, D., Grice, P., Kolb, H.C., Ley, S.V. &Madin, A. Synlett 326-327 (1990). the volcanic arcs and creates new oceanic many fundamental questions unans­ 6. Armstrong, A., Ley, S.V., Madin, A. & Mukherjee, S. crust and marginal seas through sea-floor wered. So the highest priority of Legs 127 Synlett 328-330 (1990). and 128 was recovery of basement rocks, 7. Frod, M.J., Knight, J.G., Ley, S.V. & Vile. S. Synlett spreading and faulting in the back-arc 331-336 (1990). areas between the subduction zone and which should record the earliest phases in 8. Mitchell, R.H. Biochim. biophys. Acta 415, 81-147 the continent. The Japan Sea is a large the evolution of the sea. Leg 127 drilled (1975). 9. Davies, H. G. & Green, R. H. Natural Produts Rep. 3, back-arc basin with water depths greater four locations in the Yamato and Japan 87-121 (1986). than 3,500 m, separated from the adja­ basins (sites 794, 795, 796 and 797), 10. Danishefsky, S.J., Armistead, D.M., Wincott, F.E., Selnick, H.G. & Hungate, R. J. Am. Chem. Soc. 111, cent Pacific Ocean by shallow bathymet­ where rocks that represent acoustic base­ 2967-2980 (1989). ric sills of less than 150 m depth. The ment on seismic reflection profiles were 18 NATURE· VOL 346 · 5 JULY 1990