4
Tetrahedron Letters
[2]
a) A. El-Faham, F. Albericio, Chem. Rev 2011, 111,
6557-6602; b) N. N. A. Jafar, A. N. Mohammed, A. K.
Madlool, Res. J. Pharm., Biol. Chem. Sci. 2015, 6, 906-
915; c) J. C. Sheehan, G. P. Hess, J. Am. Chem. Soc.1955,
77, 1067-1068; d) A. Williams, I. T. Ibrahim, Chem. Rev.
1981, 81, 589-636; e) Y. E. Jad, S. N. Khattab, B. G. de la
Torre, T. Govender, H. G. Kruger, A. El-Faham, F.
Albericio, Org. Biomol. Chem. 2014, 12, 8379-8385; f) L.
A. Carpino, A. El-Faham, F. Albericio, J. Org. Chem.
1995, 60, 3561-3564.
L. A. Carpino, J. Am. Chem. Soc. 1993, 115, 4397-4398.
Natl Cancer Inst Carcinog Tech Rep Ser 1978, 88, 1-131.
a) I. Abdelmoty, F. Albericio, L. A. Carpino, B. M.
Foxman, S. A. Kates, Lett. Pept. Sci. 1994, 1, 57-67; b) R.
Knorr, A. Trzeciak, W. Bannwarth, D. Gillessen,
Tetrahedron Lett. 1989, 30, 1927-1930.
a) O. Marder, F. Albericio, Chim. Oggi 2003, 21, 35-40;
b) O. Marder, Y. Shvo, F. Albericio, Chim. Oggi 2002,
20, 37-41.
a) L. A. Carpino, H. Imazumi, A. El-Faham, F. J. Ferrer,
C. Zhang, Y. Lee, B. M. Foxman, P. Henklein, C. Hanay,
C. Mugge, H. Wenschuh, J. Klose, M. Beyermann, M.
Bienert, Angew. Chem., Int. Ed. 2002, 41, 441-445; b) L.
A. Carpino, A. El-Faham, e. Albericio, Tetrahedron Lett.
1994, 35, 2279-2282.
No
.
1
Peptide
Reagent
(equiv)
P2O5 (4)
DMAP
(equiv)
0.2
Yield (%)
5a
5a
5a
5a
5a
7
67
79
83
73
78
68
77
71
72
72
2
3
HCTU (1.2)
HBTU (1.2)
DCC (3)
0
0
4
0.2
0.2
0.2
0
5
DIC (3)
[3]
[4]
[5]
6
P2O5 (4)
7
7
HCTU (1.2)
HBTU (1.2)
DCC (3)
8
7
0
[6]
[7]
9
7
0.2
0.2
10
7
DIC (3)
Table 2. Comparison with other coupling reagents
3. Conclusion
In conclusion, a cost-effective as well as mild protocol has
been developed for amide and peptide synthesis using
phosphorus pentoxide as a coupling reagent. Amides from
carboxylic acids without electron withdrawing groups were
synthesized in yields of 69-77% that were comparable to reported
methods. P2O5 was also found to useful for peptide coupling and
afforded dipeptides in 42-74% yields with minimal racemization.
The protocol is extremely attractive as the reagent is cheap, no
racemization is observed, formation of hazardous organic by-
products is minimal and isolation of the desired product is quick.
Efforts are underway to further improve the efficiency of this
reagent for synthesis of peptides.
[8]
[9]
W. Konig, R. Geiger, Chem Ber 1970, 103, 788-798.
B. Castro, J. R. Dormoy, G. Evin, C. Selve, Tetrahedron
Lett.1975, 16, 1219-1222.
[10] J. Coste, D. Le-Nguyen, B. Castro, Tetrahedron
Lett.1990, 31, 205-208.
[11] D. Hudson, J. Org. Chem. 1988, 53, 617-624.
[12] a) J. Tian, W.-C. Gao, D.-M. Zhou, C. Zhang, Org.
Lett.2012, 14, 3020-3023; b) C. Zhang, S.-S. Liu, B. Sun,
J. Tian, Org. Lett. 2015, 17, 4106-4109.
[13] H. Wissmann, H. J. Kleiner, Angew. Chem. Int. Ed. 1980,
19, 133-134.
[14] S. G. Burton, P. T. Kaye, Synth. Commun. 1989, 19,
3331-3335.
4. Acknowledgements
[15] a) I. Hayashi; T. Itikawa; K. Shimizu US patent
4,594,409, 1986.; b) J. Moye-Sherman, J. D. Stevenson
US patent 7709639, 2010.
[16] Ihara Chemical Industry, Japanese patent JP54132532,
1979.
This
research
was
supported
by
DST-SERB
(EMR/2016/007672), New Delhi, India. V. E. acknowledges
CSIR, India for his research fellowship. U.A.H. acknowledges
UGC, India for her research fellowship.
[17] a) B. Erlanger, N. Kokowsky, J. Org. Chem. 1961, 26,
2534-2536; b) G. Schramm, H. Wissmann, Chem. Ber.
1958, 91, 1073-1082.
5. Conflicts of interest
[18] a) J. A. Morales-Serna, M. A. Jaime-Vasconcelos, E.
Garcia-Rios, A. Cruz, D. Angeles-Beltran, L. Lomas-
Romero, G. E. Negron-Silva, J. Cardenas, RSC Adv.
2013, 3, 23046-23050; b) R. M. Al-Zoubi, O. Marion, D.
G. Hall, Angew. Chem., Int. Ed. 2008, 47, 2876-2879; c)
A. A. Waghmare, R. M. Hindupur, H. N. Pati, Revi. J.
Chem. 2014, 4, 53-131
The authors declare the following competing financial interest(s):
Indian patent application filing is in process. Patent application
number 201821001972.
6. References
[1]
a) N. L. Benoiton, Editor, Chemistry of Peptide Synthesis,
CRC Press, 2005; b) E. Valeur, M. Bradley, Chem. Soc.
Rev. 2009, 38, 606-631.