Nazarov Reagent: A Novel Reagent for the Synthesis of Natural Products

Biographical Sketches

Tanpreet Kaur was born in India in 1981. She received her B.Sc. degree from Kanpur University in 2001 and her M.Sc. degree in Organic Chemistry from Lucknow University in 2003. She worked as CSIR Research Intern at the Central Institute of Medicinal and Aromatic Plants, Lucknow from Jan 2004 to Jan 2006. At present, she is pursuing her Ph.D. as CSIR-JRF at the Division of Organic Chemistry (Synthesis), National Chemical Laboratory (NCL), Pune, India in the group of Dr. Asish K. Bhattacharya. Her present research is focused on design and synthesis of novel bioactive molecules and development of new synthetic methodologies.

Introduction

The Nazarov reagent (ethyl-3-oxo-4-pentenoate) is frequently used as an annulating agent in many important ­reactions. Annulation reaction comprises Michael and ­Aldol condensations and is used for the construction of molecular scaffolds which constitute the core structure of many natural products. This reagent generates different classes of natural products, mainly steroids, cardenolides, terpenoids, antibiotics and alkaloids. Modified Nazarov reagents have been used for generating diverse chemical scaffolds. [1]

Preparation

The Nazarov reagent can be prepared by the following method. These substituted Nazarov reagents are ­specific for the generation of different classes of natural products. [2]

Abstracts

(A) The 1-phenylsulfinyl and sulfonyl analogues of the Nazarov reagent are used for the highly stereoselective double Michael ­cyclization. [3a] This reagent gives the cis-decalin with high yield while other methods result in the generation of either trans-decalin or a considerable decrease in stereoselectivity. [3b]
(B) The new bicyclic Nazarov reagent is used for the convergent and expedient synthesis of naturally occurring cardioactive ­steroids. [4a] One such example is the synthesis of natural product ouabain isolated from the leaves of the plant Digitalis, which has potential for treating hypertension as well as congestive heart ­failure. [4b] This reagent was prepared from Hajos-Parrish ketone in quantitative yield. [4c]
(C) Synthesis of a precursor of (+)-preoleanatetraene has been ­accomplished using the Nazarov reagent and a chiral amine. [5a] The Nazarov reagent can also be used for the synthesis of sesquiterpenes [5b] and pentacyclic triterpenes. [5c]
(D) Hagemann’s ester can be synthesized using Nazarov reagent and enamino ester with 95% ee. [6]
(E) An efficient synthesis of SR-14139, having opioid-receptor-like activity has been achieved by the Nazarov reagent. [7]
(F) The β-thio derivative of the Nazarov reagent has been exploited for the synthesis of the cyclopentyl core of antitumor antibiotic ­viridenomycin. [8]

References

• 1 Bodalski R. Pietrusiewicz KM. Monkiewicz J. Koszuk J. Tetrahedron Lett.  1980,  21:  2287 
• 2a Streiber J. Zibuck R. Org. Synth.  1993,  71:  236 
• 2b Gaul MD. Boeckman RK. Org. Synth.  1998,  9:  432 
• 3a Spino C. Deslongchamps P. Tetrahedron Lett.  1990,  31:  3969 
• 3b Lepage O. Stone C. Deslongchamps P. Org. Lett.  2002,  4:  1091 
• 4a Chapdelaine D. Belzile J. Deslongchamps P. J. Org.Chem.  2002,  67:  5669 
• 4b Yang Z. Shannon D. Truong VL. Deslongchamps P. Org. Lett.  2002,  4:  4693 
• 4c Hajos Z. Parrish DR. Org. Synth.  1985,  63:  26 
• 5a Barrero AF. Arseniyadis S. del Moral JFQ. Herrador MM. Rosellón A. Synlett  2005,  789 
• 5b Beauhaire J. Ducrot P.-H. Tetrahedron Lett.  2002,  43:  4637 
• 5c Rouillard A. Deslongchamps P. Tetrahedron  2002,  58:  6555 
• 6 Gassama A. d’Angelo J. Cavé C. Mahuteau J. Riche C. Eur. J. Org. Chem.  2000,  3165 
• 7 Jong L. Zaveri N. Toll L. Bioorg. Med. Chem. Lett.  2004,  14:  181 
• 8 Trost BM. Jiang C. Org. Lett.  2003,  5:  1563