@article{dc3f5f2720564357a5bfdaea8a87fa2f,
title = "Synthesis of an analogue of D,L-MYO-inositol-1,2-cyclic phosphate: inhibition of phosphatidylinositol-specific phospholipase C",
abstract = "A fluorophosphonate analogue of myo-inositol-1,2-cyclic phosphate (cIP) has been synthesized: the specific, potent inhibition of a phosphatidyl inositol-specific phospholipase C (PI-PLC) by this compound is compared with inhibition by vanadate ion.",
author = "{Stewart Campbell}, A. and Thatcher, {Gregory R.J.}",
note = "Funding Information: 4. M.J Berridge & R.F. Irvine, Nafurp, 1989,$ !.I: 197. 5, T.M. Connollly, V.S. Bansal, T.E. Bruss, R.F. Irvine, P W. Majerus, .I. Binl. Chcm. 1987,m, 2146. 6. G.R.J Thatcher & R. Klugcr, Adv. Phys. Org. Chrm. 1489,E , 99. 7. J.E. Cobb & M.R. Johnson, TwxhPdron, 1991, 47, 21. 8 GM. Blackburn, Chcm. Ind. (London) lY81, 134. 9. H.W. Lee & Y. Kishi, J. Org. L{\textquoteright}hcm., 1985,5 0, 4402: Initial efforts centred vn use of penta-and t&a-O-henzylatedm yo-inositol. However reaction with carbon nucleophilesl ed to elimination products. 10. Selective NMR data is listed for all new compounds. Extensive {\textquoteleft}H-{\textquoteleft}H decoupling and COSY experimentsw ere also employedf or identification of ring protons: {\textquoteleft}H @ 400 MHz; “P @ 162MHz; 19F@ 376.5M HL; {I H} indicatesg atcd proton decoupling. 11. GM. Hlackburn & GE. Taylor, J. Orgunomet. Chem., 1988, && 55. 12. ($1 CH(:l,: “F, {{\textquoteleft}H} S=-130.4ppm( d); 31P,( {\textquoteleft}H) 6=3.19ppm( d}, I =1 01.2Ht cf. methylenecongener of (6) CDCI,: {\textquoteleft}H, P-CH, 6=56hppm (d), J; 14.3Hz.C HCI,: “P, {{\textquoteleft}HE 6-12.35ppm (s). 13. (3) D,O, {\textquoteleft}H: CZ-proton S-2.64, 11I (dm), J,, -48H2, J,,=11,5Hz, J&non ring/ring)=-5.3Hz;“ P {{\textquoteleft}H} A-12.47 (dj J,,=67.1IIz; “F {lH] J--217.29 (d); (y)“P {{\textquoteleft}H} h-12.22 (d) J,-64.1Wz; 19F{ lH} 6--217 (d) Comparison with the non-fluorinated congenerso f (8) and (7) is also useful in identification: D,O: ethylenep hosphonatea nalogueo f (8) C2-proton 6~2.59, 1H (dt), J,,=lGHz, J,,-53Hz; “P {{\textquoteleft}H) h-29.47; methylcnc phosphonatea nalogue of (2) “P {{\textquoteleft}II) 6-28.9. 14. GM, Blackburn, J.S. Cohen, Lord Todd, Tetruhedron Let&., 1964,2 873. 15. D,O: “P {{\textquoteleft}HI 6~32.54( d) J,,.=67.1Hz; 19F{ {\textquoteleft}H] 6=-203.4( cl) and; {\textquoteleft}H (Cl ring proton) (8) 6-3.65,lH (ddd) shifts to (1) 6=4.23 IH (qd)l 16. In analogy with 2-hydroxy-cycluhexanopl kospkatci somersi t is assumedt hat only the cis-acyclic phosphonatew ill readily cyclise {D .M. Brown & H.M. Higson, 1. Chem. Sot., 19.57,2034)t,h erefore the true stereoselectivityin the deprotectinns equencem ust favour the &-axial (6) over the tram-equatorial isomer (2) by 4: 1. 17. Cyctisation proceduresu sing DCC yielding the methylencp hosphonatea nalogue of (I) and cIP itself proceedi n >75% yield. However extensiveh ydrolysisi s observedo n attempteds eparationo n silica columns under similar conditions to those descrihcda bove. 18.J .J. Volwerk, M.S. Shashidhar,A . Kuppe & 0. H. Griffith, BinrhPm., 1990, 3, 8056. 19. Analogue (1) presumablyb inds to R. 0reus PI PLC as a producl analogueo f the first half-reaction. Cyclic phosphodiesterasaec tivity was not reported hy other workers (GLin, CF. Bennett, M-D. {\textquoteleft}l{\textquoteright}sai, Rinchem., 1990,3 , 27171,o ur results cast further douht on this activity. 20. A.S. Tracey & M.J. Gresser, Inorg. Chem. 1988,2 2, 2695. 21. The Natural Sciences& Engineering ResearchC ouncil of Canada and Queen{\textquoteright}s University Advisory ResearchC ommittee are thanked Lur financial support.",
year = "1991",
month = may,
day = "13",
doi = "10.1016/S0040-4039(00)79682-1",
language = "English (US)",
volume = "32",
pages = "2207--2210",
journal = "Tetrahedron Letters",
issn = "0040-4039",
publisher = "Elsevier Ltd",
number = "20",
}