Yoshito Kishi, 85

At a meeting of the Faculty of Arts and Sciences on March 5, 2024, the following tribute to the life and service of the late Yoshito Kishi was spread upon the permanent records of the Faculty.

Yoshito “Yoshi” Kishi was a renowned chemist whose scientific advances in organic chemistry were among the most impactful in the history of the field.

Although Kishi left Japan for Harvard only a few years into his independent career, he made major contributions to his native land through his mentorship of several generations of Japanese synthetic chemists, many of whom returned to Japan and became leaders of Japanese organic chemistry.

Kishi was a crown jewel and guiding force in the Harvard Department of Chemistry and Chemical Biology for 50 years.  Those who had the great fortune to have him as a colleague know well that he would have denied all of this as an essential part of his magic was his humble nature and modesty.

Kishi was one of the greatest synthetic organic chemists of his time and, indeed, of any time.  His most conspicuous research achievement was the total synthesis of a highly toxic marine natural product called palytoxin.  The isolation of palytoxin from a natural source was first reported in 1971, and it remains one of the largest and most formidably complex organic molecules ever identified.  Kishi’s was the first — and, to date, still the only — laboratory to synthesize the molecule.  His synthesis of palytoxin was years ahead of its time.  With it, Kishi essentially demonstrated that molecules of any complexity can be synthesized in the laboratory.  That synthesis is noted in nearly every organic chemistry textbook as the pinnacle of achievement, the “Mount Everest” of the field.

The field of organic synthesis is concerned with synthesizing organic molecules of interest, and Kishi had few peers in that arena.  In addition to palytoxin, his lab synthesized an astonishing array of complex natural products with names and structures known to every serious organic chemist (e.g., monensin, tetrodotoxin, and halichondrin B, among many others).  But the field of synthesis also includes discoveries of new reactions, elucidations of new strategic concepts for accessing desired molecular architectures, and, in the best of cases, applications to benefit humanity.  An ambitious researcher in the field might aspire to make meaningful advances in one or two of these aspects.  Kishi made monumental contributions in all of them.  His discovery of a cooperative effect between nickel and chromium enabled an extraordinarily powerful new method to stitch carbons together, giving rise to a class of reactions that now bears his name.  This method was ultimately applied by Kishi and by many others as a key step in numerous total syntheses.

Kishi created the field of acyclic stereocontrol, where the conformational preferences of highly flexible organic compounds could be exploited predictably for the first time to build more complex structures in geometrically precise ways.  The power of acyclic stereocontrol laid the foundation for Kishi’s synthesis of many natural products, and it is no exaggeration to say that it revolutionized the field of synthesis.  In collaborative efforts, Kishi studied the biological activity of his synthetic targets to great avail.  Drawing from his work on the marine natural product and potent anti-cancer agent halichondrin B, he conceived of and synthesized a substantially simpler unnatural molecule that would come to be known as eribulin.  That compound received FDA approval for treatment of metastatic breast cancer and is by far the most complex synthetic drug to impact human health.  Its impact on taxol-resistant cancers is substantial.  Its discovery and development relied directly on Kishi’s advances in organic synthesis, especially his catalytic diastereoselective chromium and nickel co-mediated coupling reactions and his concept of acyclic stereocontrol.

Kishi taught us the importance of fearlessness and of taking one’s own unique path regardless of what the scientific community might expect.

As a colleague, Kishi was a humble and soft-spoken leader who inspired faculty and students far more through his example than through his words.  He was universally liked and trusted as a colleague of excellent judgment and complete integrity.  His work ethic was legendary, as was his unwavering commitment to originality and scientific rigor.  Where different leading organic chemistry labs would race to be the first to synthesize a newly discovered natural product, Kishi would wait before thinking about synthesizing it.  As he told one of us, “If it is easy, someone else can do it but, if no one has succeeded after five years, then maybe it is interesting.”

Along with their educational and research missions, academic departments have no issue more important than the recruitment of new faculty.  Kishi would always ask, “Is the person we are considering someone who will see things that escape others and who will tackle them regardless of their apparent feasibility?”  Kishi’s voice is still heard in our minds, questioning the significance of new avenues of research and the fortitude of efforts to travel down these avenues.

Kishi was a primary force in the modern era of synthetic organic chemistry.  His pioneering work resulted in a new appreciation of the reach and power of this field.

Respectfully submitted,
Elias J. Corey
Stuart L. Schreiber
Eric N. Jacobsen, Chair