TY - JOUR
T1 - 2-(Tributylstannyl)-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl Alcohol
T2 - A Building Block for Photolabeling and Cross-Linking Reagents of Very High Specific Radioactivity
AU - Weber, Thomas
AU - Brunner, Josef
PY - 1995/3
Y1 - 1995/3
N2 - A general approach for the synthesis of novel, radioiodinated photolabeling and cross-linking reagents at no-carrier-added (nca) specific radioactivity (>2000 Ci/mmol) is described. In this approach, 2-(tributylstannyl)-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl alcohol 12 serves as a module which, through acylation of its alcohol function, is connected to other structural/functional elements to make the tin-containing precursor forms of the reagents. The final, radioactive compounds are then conveniently prepared in yields varying from 15—50% by electrophilic aromatic substitution of the tributylstannyl group by 125I+ generated in situ from 125I- by peracetic acid. Using this approach, we have synthesized two analogues of phosphatidylcholine (PC) (20 and 21), an analogue of ceramide (36), as well as two heterobifunctional label-transfer cross-linkers (29 and 33). PC 21, examined more closely, is a substrate of the PC-specific phospholipid exchange protein from beef liver and of phospholipase D from cabbage. The latter was utilized to enzymatically convert PC 21 into two additional phospholipids, phosphatidylserine (PS) 25 and phosphatidic acid (PA) 26. Reagents that contain this iodinated photophor also combine desirable photochemical properties. Thus, evidence is presented that they undergo efficient photolysis to generate a (singlet) carbene intermediate which inserts efficiently into hydrocarbon CH bonds. In addition, we demonstrate that the diazirine can be photolyzed in a selective manner, that is, without photodeiodination to occur to a significant extent.
AB - A general approach for the synthesis of novel, radioiodinated photolabeling and cross-linking reagents at no-carrier-added (nca) specific radioactivity (>2000 Ci/mmol) is described. In this approach, 2-(tributylstannyl)-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl alcohol 12 serves as a module which, through acylation of its alcohol function, is connected to other structural/functional elements to make the tin-containing precursor forms of the reagents. The final, radioactive compounds are then conveniently prepared in yields varying from 15—50% by electrophilic aromatic substitution of the tributylstannyl group by 125I+ generated in situ from 125I- by peracetic acid. Using this approach, we have synthesized two analogues of phosphatidylcholine (PC) (20 and 21), an analogue of ceramide (36), as well as two heterobifunctional label-transfer cross-linkers (29 and 33). PC 21, examined more closely, is a substrate of the PC-specific phospholipid exchange protein from beef liver and of phospholipase D from cabbage. The latter was utilized to enzymatically convert PC 21 into two additional phospholipids, phosphatidylserine (PS) 25 and phosphatidic acid (PA) 26. Reagents that contain this iodinated photophor also combine desirable photochemical properties. Thus, evidence is presented that they undergo efficient photolysis to generate a (singlet) carbene intermediate which inserts efficiently into hydrocarbon CH bonds. In addition, we demonstrate that the diazirine can be photolyzed in a selective manner, that is, without photodeiodination to occur to a significant extent.
UR - http://www.scopus.com/inward/record.url?scp=0028905325&partnerID=8YFLogxK
U2 - 10.1021/ja00116a013
DO - 10.1021/ja00116a013
M3 - Article
AN - SCOPUS:0028905325
SN - 0002-7863
VL - 117
SP - 3084
EP - 3095
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 11
ER -