784
Wnuk et al.
might occur as a 1,2 or 1,4-process across the conjugated dienes=enynes resulting
in the generation of new species bearing hydroxyl, keto or acyl binding sites within
the enzymes.
Oxidation of the 20,30-O-isopropylideneadenosine and Wittig treatment of
the crude 50-aldehyde with Ph3P ¼ CHTs gave 60(E)-vinyl sulfone homonucleo-
sides 1. Stannyldesulfonylation (Bu3SnH=AIBN=toluene) of 1 yielded separable
mixtures of the vinyl 60(E and Z)-stannanes 2 and 3 (B ¼ A).[3] Stille coupling[4]
[(PPh3)4Pd=THF] of vinyl 60(E)-stannane 2 (B ¼ A) with ethyl (E)-3-iodopropenoate
and deacetonization (TFA=H2O) gave dienoic ester 5 (50E=70E, s-trans; 75%),
whereas reaction with ethyl (Z)-3-iodopropenoate gave the conjugated diene 6
(50E=70Z).[5] Analogous Pd-catalyzed coupling of 60(Z)-stannane derived from uri-
dine (3, B ¼ U) with ethyl (Z)-3-iodopropenoate and deacetonization afforded 7
(50Z=70Z; 68%).a
Dienoic esters 5 and 6 produced time- and concentration-dependent inactivation
of AdoHcy hydrolase with significant decreases in the enzyme’s NADþ content.
However, 5 and 6 upon incubation with the enzyme were not metabolized suggesting
that these dienes do not show ‘‘hydrolytic substrate activity’’.
Sonogashira coupling[4] [CuI=(PPh3)2PdCl2=Et2NH] of (E)-iodohomovinyl[3]
4
(B ¼ A) with (trimethylsilyl)acetylene gave enyne 8 (71%) with expected E-stereo-
chemistry. Enyne analogues (e.g., deprotected 8) with linear triple bond attach to
C60 would require a different vicinity for binding and=or addition of enzyme-bound
water and can be further modified at C80(X ¼ halogen, COOH).
aEthyl 1,5,6,7,8-Pentadeoxy-1-(uracil-1-yl)-b-D-ribo-non-5(Z),7(Z)-dienofuranuronate (7). For
general coupling and deprotection procedures see Ref.[5]: UV max 262 nm (e 37 700), min
223 nm (e 8 000); 1H NMR (Me2SO-d6) d 1.21 (t, J ¼ 7.1 Hz, 3, CH3), 3.88 (q, J ¼ 5.5 Hz,
1, H30), 4.08–4.16 (m, 3, H20 & CH2), 4.79 (dd, J ¼ 5.9, 8.8 Hz, 1, H40), 5.40 (d, J ¼ 6.0 Hz, 1,
OH30), 5.58 (d, J ¼ 5.6 Hz, 1, OH20), 5.66 (d, J ¼ 8.1 Hz, 1, H5), 5.76 (d, J ¼ 4.3 Hz, 1,
H10), 5.80 (d, J ¼ 11.5 Hz, 1, H80), 6.06 (dd, J ¼ 9.0, 11,2 Hz, 1, H50), 7.08 (‘‘t’’, J ¼ 11.7 Hz,
1, H70), 7.33 (‘‘t’’, J ¼ 11.5 Hz, 1, H60), 7.66 (d, J ¼ 8.1 Hz, 1, H6), 11.40 (br s, 1, NH); 13C
NMR (Me2SO-d6) d 14.98, 60.65, 73.68 & 75.00 (C20 & C30), 79.27 (C40), 90.35 (C10),
102.90 (C5), 120.13 (C80), 127.14 (C60), 138.40 & 139.47 (C50 & C6), 142.15 (C70),
151.45 (C2), 163.95 (C4), 166.35 (C90); MS (CI) m=z 339 (MHþ). Anal. Calcd for
C15H18N2O7 (338.33): C, 53.25; H, 5.36; N, 8.28. Found: C, 53.62; H, 5.61; N, 8.01.