Colleagues of John A. Porco Jr. single him out as a "highly accomplished designer and conductor of the total synthesis of complex, biologically relevant molecules," as well as for his "uncanny ability to bring out the best in everyone he touches."
Porco, 45, received a Ph.D. from Harvard University in 1992. He went on to do postdoctoral work at Scripps Research Institute before joining the venture capital firm Avalon Technologies in 1993. The venture capital work to develop companies was an interesting way to apply his science skills, he says. But the bench called him back, and in 1995 he helped form Argonaut Technologies to develop instrumentation for parallel synthesis.
Porco's passion, however, is natural product synthesis, and in 1999 he joined the Boston University chemistry department to pursue a research program in that area. Since then he and his colleagues have synthesized more than 25 complex natural products. One compound of particular note is (+)-hexacyclinol, an antiproliferative metabolite that had been isolated from a fungus in 2002 and was the subject of some controversy over its structure (C&EN, July 31, 2006, page 11).
Porco and colleagues designed a synthesis around a highly stereoselective Diels-Alder dimerization of an epoxyquinol monomer, followed by an intramolecular acid-catalyzed cyclization (Angew. Chem. Int. Ed. 2006, 45, 5790). When the resulting compound had a 1H NMR spectrum that matched that of the original isolate, the structural debate was put to rest.
At the same time as the hexacylinol work, Porco was also working on the total synthesis of (–)-kinamycin C, one of a family of diazobenzofluorene antibiotics that were first isolated in 1970. Porco and graduate student Xiaoguang Lei accomplished the synthesis through an asymmetric nucleophilic epoxidation to establish the correct stereochemistry of the compound's highly oxygenated D ring (J. Am. Chem. Soc. 2006, 128, 14790). They also took the approach of installing a highly reactive diazo group very late in the synthesis.
Porco is now working on synthetic strategies that involve dearomatization—using flat, aromatic rings as scaffolds before removing the aromaticity to form a more complex structure. Porco also turns to biosynthesis for inspiration when grappling with new synthetic methods to prepare elusive natural products and analogs.
Complementing his work on natural product synthesis, Porco spearheaded the establishment and is now director of the Boston University Chemical Methodology & Library Development Center (CMLD-BU), a National Institutes of Health Center of Excellence. One current project involves high-throughput screening to identify new chemical reactions that might be useful for synthesis (J. Am. Chem. Soc. 2007, 129, 1413).
Porco is one of the leaders of natural products synthesis, says Samuel J. Danishefsky, a professor of chemistry at Columbia University and the director of the Laboratory for Bioorganic Chemistry at Memorial Sloan-Kettering Cancer Center, in New York City. He praises Porco's "ability to orchestrate the assembly of complex target systems." And although Danishefsky is not typically a fan of chemical libraries, he nonetheless commends Porco's work at CMLD-BU for "practicing high standards of chemical synthesis and producing pure compounds in reasonable amounts."
John K. Snyder, one of Porco's colleagues in the chemistry department at BU, adds that Porco "can build a team of researchers and keep it running smoothly, something not always very easy with the different personalities that exist within a department."