Organic Letters
Letter
and Centaur Pharmaceuticals, Mumbai, for providing spectral
details of quinagolide.
Scheme 5. Completion of the Total Synthesis
REFERENCES
■
(1) (a) Somei, M.; Yokoyama, Y.; Murakami, Y.; Ninomiya, I.;
Kiguchi, T.; Naito, T. Recent Synthetic Studies on the Ergot Alkaloids
and Related Compounds. In The Alkaloids, Vol. 54; Cordell, G. A.,
Ed.; Academic Press: San Diego, CA, 2000; p 191. (b) Krogsgaard-
Larsen, N.; Jensen, A. A.; Schrøder, T. J.; Christoffersen, C. T.;
Kehler, J. J. Med. Chem. 2014, 57, 5823. (c) Sinz, A. Pharm. Unserer
Zeit 2008, 37, 306.
(2) Nordmann, R.; Petcher, T. J. J. Med. Chem. 1985, 28, 367.
(3) Di Sarno, A.; Landi, M. L.; Marzullo, P.; Di Somma, C.;
Pivonello, R.; Cerbone, R.; Lombardi, G.; Colao, A. Clin. Endocrinol.
2000, 53, 53.
(4) Banziger, M.; Cercus, J.; Stampfer, W.; Sunay, U. Org. Process
Res. Dev. 2000, 4, 460.
PPTS-catalyzed one-pot acetal deprotection, followed by a
diastereoselective Henry reaction, which enables construction
of required trans geometry, and CAN-mediated regioselective
azidoalkoxylation of enol ether, which allows quick access to
the piperidine ring, as well as nitrogen-containing side chain of
quinagolide, are noteworthy features. A diastereoselective
Henry reaction using PPTS to fix three contiguous stereo-
centers on tetrahydronaphthalene and synthesis of 3-
azidopiperidines using CAN mediated regioselective azidoal-
koxylation of enol ether are important findings of this synthesis
and hopefully will find more applications in total synthesis in
the near future. The enantioselective total synthesis of
quinagolide is currently underway in our laboratory.
(5) Nordmann, R.; Widmer, A. J. Med. Chem. 1985, 28, 1540.
(6) Selected publications from this group: (a) Chavan, S. P.;
Tejwani, R. B.; Ravindranathan, T. J. Org. Chem. 2001, 66, 6197.
(b) Chavan, S. P.; Ramakrishna, G.; Gonnade, R. G.; Bhadbhade, M.
M. Tetrahedron Lett. 2004, 45, 7307. (c) Chavan, S. P.; Chittiboyina,
A. G.; Ravindranathan, T.; Kamat, S. K.; Kalkote, U. R. J. Org. Chem.
2005, 70, 1901. (d) Chavan, S. P.; Lasonkar, P. B.; Chavan, P. N.
Tetrahedron: Asymmetry 2013, 24, 1473. (e) Chavan, S. P.; Chavan, P.
N.; Gonnade, R. G. RSC Adv. 2014, 4, 62281. (f) Chavan, S. P.;
Chavan, P. N.; Khairnar, L. B. RSC Adv. 2014, 4, 11417. (g) Chavan,
S. P.; Pawar, K. P.; Garai, S. RSC Adv. 2014, 4, 14468.
(7) Ortiz, G. X.; Kang, B. J.; Wang, Q. J. Org. Chem. 2014, 79, 571
and references cited therein .
(8) (a) Norton Matos, M. R.; Afonso, C. A. M; Batey, R. A.
Tetrahedron Lett. 2001, 42, 7007. (b) Le Corre, L.; Dhimane, H.
Tetrahedron Lett. 2005, 46, 7495. (c) Le Corre, L.; Kizirian, J. C.;
Levraud, C.; Boucher, J. L.; Bonnet, V.; Dhimane, H. Org. Biomol.
Chem. 2008, 6, 3388.
(9) Chavan, S. P.; Subbarao, Y. T. Tetrahedron Lett. 1999, 40, 5073.
(10) Andruszkiewicz, R.; Silverman, R. B. Synthesis 1989, 1989, 953.
(11) Reduction of nitrostyrene 7c using known literature procedures
leads to the inseparable mixture of cis and trans nitro-ester in variable
ratio.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
NMR spectra, 2D-NMR analysis, detailed experimental
procedures, and characterization data (PDF)
(12) Representative natural products having substituted tetrahy-
dronaphthalene core: (a) Wang, K. W.; Mao, J. S.; Tai, Y. P.; Pan, Y. J.
Bioorg. Med. Chem. Lett. 2006, 16, 2274. (b) Cueva, J. P.; Gallarado-
Godoy, A.; Juncosa, J. I., Jr.; Vidi, P. A.; Lill, M. A.; Watts, V. J.;
Nichols, D. E. J. Med. Chem. 2011, 54, 5508. (c) Devkota, K. P.;
Covell, D.; Ransom, T.; McMahon, J. B.; Beutler, J. A. J. Nat. Prod.
2013, 76, 710. (d) Izawa, M.; Kimata, S.; Maeda, A.; Kawasaki, T.;
Hayakawa, Y. J. Antibiot. 2014, 67, 159. (e) Zhang, Y. A.; Liu, Q.;
Wang, C.; Jia, Y. Org. Lett. 2013, 15, 3662. (f) Chaudhuri, S.; Bhunia,
S.; Roy, A.; Das, M. K.; Bisai, A. Org. Lett. 2018, 20, 288.
(13) (a) Barclay, T. K.; Santillan, A. J.; Tang, L. Y.; Venkatesan, H.;
Wolin, R. L. PCT International Patent Application No. 2005044810,
May 19, 2005. (b) Ko, K. Y.; Wagner, S.; Yang, S. H.; Furkert, D. P.;
Brimble, M. A. J. Org. Chem. 2015, 80, 8631.
(14) (a) Basha, A.; Orlando, J.; Weinreb, S. M. Synth. Commun.
1977, 7, 549. (b) Sparks, S. M.; Gutierrez, A. J.; Shea, K. J. J. Org.
Chem. 2003, 68, 5274.
(15) In the NOESY spectrum of compound 5a, there is no NOE
observed between proton at azide centre and βH (with respect to the
azide center) at the ring junction, indicating that they are trans to each
other.
Accession Codes
CCDC 1846322 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
(16) (a) Staudinger, H.; Meyer, J. Helv. Chim. Acta 1919, 2, 635.
(b) Cochi, A.; Gomez Pardo, D.; Cossy, J. Org. Lett. 2011, 13, 4442.
(17) Node, M.; Nishide, K.; Fuji, K.; Fujita, E. J. Org. Chem. 1980,
45, 4275.
ACKNOWLEDGMENTS
■
A.L.K. thanks UGC, New Delhi, for the award of a research
fellowship. The authors thank CSIR, New Delhi for financial
support as part of XII Year Plan Programme under the title
ORIGIN (No. CSC-0108) and ACT (No. CSC-0301). We
also thank Dr. P. R. Rajamohanan for help in 2D NMR
analysis, Dr. H. B. Borate for carefully evaluating manuscript,
D
Org. Lett. XXXX, XXX, XXX−XXX