Vanadium(II)‐ and Niobium(III)‐Induced, Diastereoselective Pinacol Coupling of Peptide Aldehydes to C₂‐Symmetrical HIV‐Protease Inhibitors

Abstract

Potent inhibitors of HIV‐protease such as 1 can be produced on a kilogram scale by diastereoselective, reductive dimerization of homochiral peptide aldehydes. This is made possible by the use of niobium catalysts or vanadium catalysts generated in situ in the crucial reaction step. aryl = 1‐naphthyl.

Intramolecular Chromium(II)-Catalyzed Pinacol Cross Coupling of 2-Methylene-α,ω-dicarbonyls

“…1,2-Diols can be generated in general by bishydroxylation of olefinic double bonds 2 or reductive coupling of carbonyl compounds. 3 The last method plays an important role in the synthesis of HIV-protease inhibitors 4 and natural products 5 such as Taxol 6 and Cotylenol 7 and their derivates. For their synthesis this reaction has to be performed in a diastereoselective fashion.…”

Construction of C-C bonds via photoreductive coupling of ketones and aldehydes in the metal-organic-framework MFM-300(Cr)

“…Aldehydes and ketones are among the most valuable organic compounds that can be obtained from renewable resources, such as biomass, in large scale. Reductive coupling of aldehydes and ketones offers a promising route to the synthesis of 1,2-diols, which are important structural motifs in a broad range of natural products 3 , pharmaceuticals 4 , protease inhibitor 5 , peptidomimetics 6 and polymers 7 , and are widely used as chiral ligands and auxiliaries in organic reactions 8 . However, this is a very challenging photochemical process owing to the highly negative reduction potential of carbonyl compounds, particularly for ketones [e.g., acetophenone: E 1/2red = −1.79 V vs. normalised hydrogen electrode (NHE) 9 ] and to date, success has only been achieved in exceptional cases 9 – 14 .…”

Low-Valent Titanium-Mediated Reductive Coupling of Carbonyl Compounds

“…These reviews show that intra-or intermolecular coupling of a wide variety of carbonyl compounds, such as aldehydes, ketones, acylsilanes, ketoesters, and oxoamides, can be applied to provide a remarkably diverse array of synthetic and natural products. Hence pinacol and McMurry coupling reactions constitute two of the most powerful methods for constructing carboncarbon bonds, and have served as the key step in the synthesis of various natural products and pharmacologicallyactive compounds, including taxol [11][12][13][14][15], sarcophytol B [16], periplanone C [17], crassin [18], C 2 -symmetrical HIV protease inhibitors [19], and Z-tamoxifen [20][21][22]. The McMurry reaction has also been used to produce a variety of strained or sterically hindered olefins, macrocycles, polymers, and heterocyles [5][6][7][8][9][10].…”