A New Classic Arrives

By Jason Socrates Bardi

A few years ago, Scott Snyder was settling into the fall semester of his senior year at Williams College in Williamstown, Massachusetts, and his thoughts were some 3,000 miles away.

Surrounded by the gorgeous fall foliage on the Williams campus near the Vermont and New York borders, Snyder was nevertheless engrossed in a book that was written a few years prior on the temperate, California campus of The Scripps Research Institute (TSRI).

Titled Classics in Total Synthesis by TSRI's K.C. Nicolaou and Erik J. Sorensen (now at Princeton University), the book detailed several modern examples of the "total synthesis" or construction of an organic compound from precursor molecules in the laboratory—research that has often been compared to Herculean tasks.

"Reading this book was a strong driving force for me to come to TSRI," says Snyder. Presently a fifth year graduate student in TSRI's Kellogg School of Science and Technology, he immediately chose to study synthetic organic chemistry under Nicolaou, who is chair of TSRI's Department of Chemistry and holds the Aline W. and L.S. Skaggs Professorship of Chemical Biology and the Darlene Shiley Chair in Chemistry.

Now, four years later, Snyder is coauthor with Nicolaou of a new book—Classics in Total Synthesis II (2003, Wiley)—the sequel to the text that first steered his course.

Milestones in Science and Publishing

The total synthesis of organic compounds dates back to 1828, when Friedrich Wohler first combined cyanic acid with ammonium carbonate in a test tube to make urea. But it took much of the 20th century for the field to grow to its present, powerful state.

In the foreword to the new book, Nobel laureate E.J. Corey of Harvard University, who was Nicolaou's postdoctoral advisor, says that the first book "...stands as a milestone to mark the closing of the 20th century, which encompassed both the birth of the field and its growth to one of the most intellectually fulfilling and practically important areas of modern science."

Classics in Total Synthesis II takes up where the previous volume left off, and covers the reactions and synthetic methods that have come of age since the publication of Classics in Total Synthesis.

One of the new compounds featured is the anticancer compound diazonamide A, which Nicolaou, Snyder, and several members of the group synthesized last year. A picture of this natural product and the sea creature from which it was discovered, the colonial ascidian diazona angulata, adorns the cover.

Twenty other complex natural products are also described in Classics in Total Synthesis II, including several others from the Nicolaou group, two molecules tackled by TSRI investigator Dale L. Boger, and one synthesized by former TSRI Professor Erik J. Sorensen. Mention is also made of several important synthetic discoveries that have emanated locally from the TSRI groups of M. Reza Ghadiri, Kim D. Janda, Subhash Sinha, and K. Barry Sharpless.

For each compound, the book carefully describes the synthetic route from chemical precursors to the final product, focusing special attention on the novel strategies and tactics that were employed. Each chapter ends with a lengthy bibliography, which is intended to enhance the pedagogic value of the book to all of its readers—professors, graduate students, advanced undergraduates, and researchers in chemical industry—by providing primary references for further enrichment.

Ultimately, say Nicolaou and Snyder, the goal is not only to present these classic examples as historical achievements of what can be accomplished in the laboratory, but, hopefully, to inspire the next generation of synthetic chemists on whose shoulders lie the responsibility of pushing the boundaries of the field even further.

A Sign of Things to Come

Last month, Nicolaou and Snyder held a book signing sponsored by their publishers at the American Chemical Society meeting in New York City. They were met with lines of students and teachers eagerly waiting to get their hands on an advanced copy of Classics in Total Synthesis II.

Nicolaou and Snyder joke that while it took a year and a half for them to put the book together, they sold out all their advanced copies in less than half an hour.

The success of this signing could not have been more thrilling for Nicolaou and Snyder, because most of the copies were purchased by students who were attending the meeting. It was in the spirit of educating these very students that Nicolaou and Snyder picked up their pens in the first place.

"It's important for us [as scientists] to motivate, inspire, educate and train," says Nicolaou. "We must think about the next generation of scientists."

Copies of Classics in Total Synthesis II will be available from the publisher, Wiley-VCH, and should be delivered by the end of October.



Professor K.C. Nicolaou (right) and graduate student Scott Snyder (center) sign copies of their new book at the American Chemical Society meeting.





Classics in Total Synthesis II covers reactions and synthetic methods that have recently come of age.