The Scripps team, led by chemist Phil Baran, describes in Nature how it achieved the preparative-scale, enantioselective, total synthesis of members of the hapalindole, fischerindole, welwitindolinone and ambiguine families of marine natural products without using a single protecting group of compounds. The researchers believe the concepts and principles demonstrated in Nature should be applicable to a wide range of marine and terrestrial natural products, with the potential both to reduce significantly production costs for natural products and open the door to wider use of these products in drug discovery. Organic chemistry textbooks have long insisted that skirting protecting groups is "like avoiding death and taxes," Baran commented. Protecting groups are additional compounds used by chemists to shield reactive portions of a molecule during specific stages of product synthesis. The drawback is that each protecting group adds at least two steps to the process, while the groups themselves have reactivity of their own that must be controlled to prevent adverse reactions. Rather than assuming that reactive portions of the molecules needed to be protected during synthesis, the Scripps team found ways of incorporating this reactivity into the overall product-synthesis scheme. It did so by designing a variety of chemical reactions that maximised the bonding of carbon atoms between different molecules. Conventional thinking dictated that "the way to solve these types of problems is to protect functionality rather than to try to embrace it," Baran noted. Yet in several cases the Scripps team managed to synthesise gram quantities of natural products in fewer than 10 steps, whereas traditional synthesis using protecting groups can take as many as 30 steps to generate milligrams of product. Identifying a reasonably economic means of production for marine and other natural products is "typically one of the most challenging hurdles in a potential drug's commercial development," the Scripps institute observed. Moreover, despite the natural roots of drugs ranging from aspirin to the anticancer Taxol (paclitaxel), and the persistent concerns over waning R&D productivity in the pharmaceutical industry, the complexity of synthesising natural compounds has made some companies reluctant to pursue this line of drug discovery, it added. Baran's team has focused its efforts on marine natural products because they are a rich source of bioactivity yet tend to be exceptionally complex - and usually difficult to collect as well. By demonstrating that the route to synthesis of these compounds can be markedly shortened by eliminating protecting groups, the Scripps researchers may help to persuade the pharmaceutical industry that the further reaches of natural product research are not so inaccessible.