Organic Chemistry Portal
Organic Chemistry Highlights

Monday, May 30, 2016
Douglass F. Taber
University of Delaware

Functional Group Interconversion: The Danishefsky Synthesis of Granulocyte Colony-Stimulating Factor

Wenjun Zhang of the University of California, Berkeley uncovered (ACS Catal. 2015, 5, 7091. DOI: 10.1021/acscatal.5b01842) an E. coli enzyme that efficiently decarboxylated a medium-chain fatty acid 1 to the terminal alkene 2. Courtney C. Aldrich of the University of Minnesota established (Angew. Chem. Int. Ed. 2015, 54, 13041. DOI: 10.1002/anie.201506263) fully catalytic conditions for the Mitsunobu coupling of 3 with 4 to give 7. Agnieszka Wojtkielewicz of the University of Bialystok created in situ (Synlett 2015, 26, 2288. DOI: 10.1055/s-0034-1381060) an aminoalane that converted the lactone 8 to the hydroxy nitrile 9.

Flurocarbons are generally considered to be chemically inert. Tamotsu Takahashi of Hokkaido University reported (Org. Lett. 2015, 17, 5942. DOI: 10.1021/acs.orglett.5b02589) conditions for the conversion of the fluoride 10 to the iodide 11. Chlorides and bromides could also be prepared.

Ming Bao of the Dalian University of Technology developed (Chem. Commun. 2015, 51, 10714. DOI: 10.1039/C5CC03429A) a one-pot protocol for the conversion of a bromide 12 to the nitrile 13 having the same number of carbons. Patrick H. Dussault of the University of Nebraska optimized (J. Org. Chem. 2015, 80, 12100. DOI: 10.1021/acs.joc.5b02043) the hydroperoxide 15, that could be coupled with an activated alcohol 14 to give an intermediate peroxide, that could then be coupled with a nucleophilic organometallic 16 to give the ether 17. Bing-Tao Guan of Nankai University showed (Chem. Commun. 2015, 51, 17596. DOI: 10.1039/C5CC07454A) that on oxidation in the presence of acetic anhydride, the tertiary amine 18 could be converted to the amide 19.

Steven P. Nolan of the University of St. Andrews observed (ACS Catal. 2015, 5, 6918. DOI: 10.1021/acscatal.5b02090) remarkable regioselectivity in the Au-mediated hydrocarboxylation of 20 to 21. This opens what promises to be a general route to α-aryl ketones.

Joseph Moran of the Université de Strasbourg observed (J. Am. Chem. Soc. 2015, 137, 9555. DOI: 10.1021/jacs.5b06055) remarkable selectivity in the conversion of the diol 22 to the azido alcohol 23. Kami L. Hull of the University of Illinois, Urbana-Champaign established conditions (J. Am. Chem. Soc. 2015, 137, 13748. DOI: 10.1021/jacs.5b08500) for the selective hydroamination of the diene 24 to the diamine 26.

Bruce H. Lipshutz of the University of California, Santa Barbara extended (Org. Lett. 2015, 17, 3968. DOI: 10.1021/acs.orglett.5b01812) to amide and peptide formation his remarkable work on "nanoreactors" formed from aqueous suspensions of surfactant, coupling 27 with 28 in the presence of 29 to give 30. Native chemical ligation, developed with cysteine, can also be carried out with selenocysteine. Norman Metanis of the Hebrew University of Jerusalem established (Chem. Sci. 2015, 6, 6207. DOI: 10.1039/C5SC02528A) conditions for the deselenization of 31 to 32 that left cysteines intact. Further, under aerobic conditions, the product was not the alanine as illustrated, but the serine.

The coupling of longer peptide fragments is still a major synthetic challenge. Andrew G. Roberts and Samuel J. Danishefsky of the Sloan Kettering Institute for Cancer Research found (J. Am. Chem. Soc. 2015, 137, 13167. DOI: 10.1021/jacs.5b08754) that a thioacid/isonitrile approach was effective, enabling the coupling of 33 with 34 to give 35, leading to the total synthesis of the 174-residue human granulocyte colony-stimulating factor (36).

D. F. Taber, Org. Chem. Highlights 2016, May 30.