Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
As a graduate student, I ended my PhD work on this very topic with van Tamelen. My experience on the cyclase project greatly influenced my views of chemistry and the chemistry of life itself, and it still does today. I think of this bizarre process discovered by life, as it got to cholesterol, as one of the greatest stories to alert humankind that we are deluded in our aims to discover life’s most profound, even just physics and chemistry mysteries, let alone our endless, fanciful worries[2,3].
Returning to direct comments on Krief et al. work here, I found it fascinating and profound scientifically. More than most other chemists, except for Hisashi Yamamoto, I can say how tough synthetic chemistry stands behind this work[5,6]. Not only are the steps fraught with steps that never give perfect yields, but they are also deep into overlapping physical properties of the product mixtures, and then they need to get each component of mixtures separated and then on very small scales assigned unambiguously.
This takes concentration and effort beyond any challenges I have taken on since graduate school. This is important scientific research that has been conducted without taking any shortcuts. The scholarship is superb. The paper is illuminating, thought-provoking, and its methodology is a model for others to follow.
Chemical Synthesis is so fortunate that its debut motivated Prof. Krief and his associate to revive this research. Moreover, I would like to close now by giving the authors my most sincere and highest congratulations!
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1. Tamelen EE, Sharpless KB, Hanzlik R, Clayton RB, Burlingame AL, Wszolek PC. Enzymic cyclization of trans,trans,trans-18,19-dihydrosqualene 2,3-oxide. J Am Chem Soc 1967;89:7150-1.DOIPubMed
2. Bergmann W, Domsky II. STEROLS OF SOME INVERTEBRATES*. Ann N Y Acad Sci 1960;90:906-9.DOI
3. Ourisson G, Nakatani Y. The terpenoid theory of the origin of cellular life: the evolution of terpenoids to cholesterol. Chem Biol 1994;1:11-23.DOIPubMed
4. Krief A, Sable R, Ronvaux A, Dumont W, Sandra P, David F. Schizophrenic behavior of 2,3-Oxidosqualene Sterol Cyclase from pig liver towards 2,3-oxidosqualene analogues. Chem Synth 2021;1:6.DOI
5. Corey EJ, Ortiz de Montellano PR, Yamamoto H. Separation of the cyclization and rearrangement processes of sterol biosynthesis. Enzymic formation of a protosterol derivative. J Am Chem Soc 1968;90:6254-5.DOI
6. Corey E, Yamamoto H. Correlation of a protosterol from 20,21-dehydro-2,3-oxidosqualene and 2,3-oxidosqualene-sterol cyclase with dihydrolanosterol. Tetrahedron Lett 1970;11:2385-6.DOIPubMed
Sharpless KB. The “fittest sterol” - origin mysteries still fascinate. Chem Synth 2021;1:8. http://dx.doi.org/10.20517/cs.2021.13
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