Stereochemistry of samarcandin-type sesquiterpenoid coumarins. Crystal structures of feshurin and nevskin

1
2
H
HO
OR
OH
H
OH
OR
HO
H
OR
HO
OH
3
4
OR
OH
H
HO
H
HO
OR
OH
H
OH
HO
OR
H
HO
OR
OH
5
6
7
8
1: 1
cR,2cS,6cS, ([D]
D
+30
q (C
2
H
5
OH); 2: 1
cR,2cR,6cS, [D]
D
–51
q; 3: 1cR,2cS,6cR, [D]
D
+27
q (C
2
H
5
OH); 4: 1
cR,2cR,6cR, [D]
D
–79
q (CHCl
3
)
5: 1
cS,2cS,6cS, [D]
D
–55
q (CHCl
3
); 6: 1
cS,2cR,6cS; 7: 1cS,2cS,6cR; 8: 1cS,2cR,6cR, [D]
D
+32
q (C
2
H
5
OH)
DOI 10.1007/s10600-015-1253-4

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243
Errors of a different type are also encountered in the literature. For example, Egyptian researchers isolated from F. sinaica a
samarcandin stereomer and reported the discovery of its “new” diastereomer based on mass, PMR, 
13
C NMR, and 1D and 2D
NMR spectra [5]. The researchers confirmed this based on the orientations of substituents on asymmetric centers of the
bicyclic system. However, the aforementioned NMR spectroscopic methods determined only the relative configurations of
the chiral centers. Therefore, the proposed structure of the new diastereomer could have the 1
cR,2cR,6cS,9S,10R or
1
cS,2cS,6cR,9R,10S configuration. The latter configuration was equivalent to that observed in a known diastereomer,
episamarcandin (1
cS,2cS,6cR,9R,10S). Therefore, such a report was incorrect without establishing the absolute configuration
of the isolated diastereomer because spectral data of episamarcandin and the new diastereomer were theoretically identical.
The crystal and molecular structures of feshurin (2) and nevskin (4) were established and their absolute configurations
were confirmed by the present XSA (using Cu K
D-radiation). We used the completed XSA to correct the chemical structures
of the eight natural samarcandin diastereomers and the absolute configurations of their chiral centers [samarcandin (1), feshurin
(2), isosamarcandin (3), nevskin (4), fepaldin (5), deacetylkellerin (6), episamarcandin (7), and ferucrin (8)].
Figure 1 shows the molecular structures of 2 and 4 from the XSA in similar projections. They are umbelliferone
ethers. The steric structures of 2 and 4 differ visually in the C6
c configuration (Fig. 1). The chiral atoms have the configurations
1
cR,2cR,6cS [Flack parameter x = 0.2(3)] and 1cR,2cR,6cR [x = 0.1(2)]. The Huft parameters (y) were also calculated in order
to assess the absolute configurations because these compounds did not contain atoms heavier than oxygen [6]. The values
were y = 0.1(2) and 0.3(1) for 2 and 4, respectively. As expected, chiral atoms 9
cR and 10cS in both molecules retained their
absolute configurations.
The C2
c hydroxyls in 2 and 4 had the 
D-axial orientation whereas the C6c hydroxyls were E-axial and D-equatorial,
respectively. The C9
c methyls were 
D-axial; the C1c–C13c bonds (in the umbelliferone part), D-equatorial. The condensed six-
membered rings were trans-fused and had the chair conformation. The umbelliferone parts were planar within 0.022 and 0.023 A
°
for 2 and 4, respectively. They were positioned almost identically relative to the sesquiterpene part in both molecules.
The hydroxyls (O4–H and O5–H) of the basic molecule in the crystal structure of 2 participated in forming
intermolecular H-bonds with the coumarin oxygen atoms (O2 and O1) that were transformed by different symmetry operators
(Table 1). However, the H-bonds were rather weak according to the D…A distances given in Table 1.
The hydroxyl (O4–H) of the basic molecule in the crystal structure of 4 was bonded through an intermolecular
H-bond to the oxygen (O5) of another hydroxyl transformed by 2
1
symmetry. Also, the O5 hydroxyl H atom of the basic
molecule approached the carbonyl oxygen (O2) of the umbelliferone part of a transformed molecule. Table 1 lists the
intermolecular H-bond parameters.
TABLE 1. Hydrogen Bonds in Crystal Structures of 2 and 4 (d, distance; D, donor; A, acceptor)
Compound 
D–H … A 
d (D-Í), A
°
d (Í…A), A
°
d (D…A), A
°
<(DHA), 
deg 
Symmetry