UU | BMC | Bioorg. Chem. |

A new seven-parameter generalized Karplus-type relation
between proton coupling constants and the corresponding H-C-C-F
and H-C-C-H torsion angles has been developed
[Refs. 281 and 284].

**1. Correlation between vicinal
proton fluorine coupling constants and the corresponding H-C-C-F
[Ref. 281]**

The optimum values of the seven parameters were determined using a data
set consisting of 57 ^{3}J_{HF} values and the corresponding
F_{HF}
torsion angles (ranging from cis, gauche, and trans regions) based upon
*ab
initio* structures as well as on the conformational analysis of temperature-dependent
^{3}J_{HH}
of monofluorinated nucleosides **1**-**11**, which were also complemented
with the data from conformationally fixed compounds **12**-**22**

**Scheme 1. Compounds 1-17 used for the
parameterization of Karplus equation (Sections C-G)**

The best fit generalized Karplus-type equation shows the difference between input and back-calculated

**Scheme 2. Compounds 18-23 which ^{3}J_{HF}
are used for parameterization of Karplus equation (Section C-G) and compounds
24-29 where newly parametrized Karplus equation os applied (Section C-G).**

**2. NMR conformation and
correlation between proton coupling constants and the corresponding
H-C-C-H of**
** (-)-a-D-Aristeromycin
and its 2'-Deoxy and 3'-Deoxy counterparts in aqueous solution [Ref.
284].**

The solution conformations of aristeromycin (**1**), 2'-deoxyaristeromycin
(**2**), and 3'-deoxyaristeromycin (**3**) have been determined from
an integrated analysis of X-ray (for **1 **only), NMR data (i.e., ^{3}J_{HH}
coupling constants), and *ab initio* calculations. Newly developed
A and B sets of parameters correlating the H-C-C-H torsions to the endocyclic
torsions based on the *ab initio* optimised structures of **1**-**3**
have been subsequently used to interpret the time-averaged ^{3}J_{HH}
couplings using the program PSEUROT. The discrepancy found between the
X-ray crystal structure of aristeromycin (**1**) and its structure calculated
by NMR-PSEUROT conformational analysis prompted us to reparametrize the
Karplus equation implemented in the PSEUROT program by using torsion angles
derived from solid-state geometries of conformationally constrained nucleosides
and their corresponding experimental ^{3}J_{HH}.
The precision of our reparametrized Karplus-type equation (rms error )
0.40 Hz) became comparable to that expected for the standard Haasnoot-Altona
Karplus (0.48 Hz) equation. The results of the PSEUROT analyses performed
with the standard Haasnoot-Altona Karplus equation are also very comparable
in terms of geometry with those based on our reparametrized equation. Both
series of PSEUROT analyses suggest that the predominant conformation of
the cyclopentane ring in 1-3 is defined by 128° <* P *<
140° for **1**, 105° < *P* < 116° for **2**,
and 118° <* P* < 127° for **3,** with the puckering
amplitude in the range from 34° to 40° for **1**-**3**. However,
PSEUROT analyses based on our Karplus equation produced a smaller rms error
of 0.14 Hz and D*J*_{max}
error of 0.5 Hz than those performed with the standard Haasnoot-Altona
equation. This work therefore highlights two important points:
(i) the solution-and the solid-state structures of aristeromycin (**1**)
are indeed different, and (ii) the close similarity
of geometries derived from Haasnoot-Altona's equation or from our Karplus
equation suggest that the solution structures for **1**-**3** are
correctly defined.

**Scheme 3. Compounds used for the parameterization
of Karplus equation**

Dep't of Bioorg. Chem. | Last mod.: Feb. 27, 2007 | URL http://www.boc.uu.se/ |