In light of the correlation data from COSY (between H-31
and H-31a) and HMBC (H-31/31a to C-23/24, and from
NH to C-23) experiments (SI, Figure S3), we deduced that
the L-Ala methyl group in 2 was replaced by a cyclopro-
pane in 3. ROESY correlations confirmed that 2 and 3
shared the same relative configuration (SI, Figure S3).
Comparisons of the ECD and VCD data of 3 with the
calculated spectra (Figure 4, B and D) provided the ab-
solute configuration of 3(5R,7S,8R,9R,10R,13S,14S,16S,22S).
C34H44N2O6, respectively, based on HRESIMS. Both
compounds exhibited 13C NMR resonances similar to 2
and 3 (Table 1) with the exceptions being that, in each
instance, the C-1 and C-2 olefinic methines were replaced
by methylenes. Further evidence for the increased satura-
1
tion at these positions was afforded by H NMR, which
revealed new proton resonances at δ1.70, 1.85, 2.54, and
2.80, as well as δ 1.70, 1.82, 2.54, and 2.79 for 4 and 5,
respectively. Confirmation of the planar structures of 4
and 5 was provided by analysis of COSY and HMBC
correlation data (SI, Figure S3) that demonstrated these
compounds shared the same atom arrangements as
their unsaturated analogs. Additionally, ROESY correla-
tion data (SI, Figure S3) indicated that 4 and 5 posses-
sed the same relative configurations as 2 and 3, respec-
tively. Finally, quantum chemical ECD calculations (SI,
Figure S4) enabled us to independently establish the
absolute configurations of 4 (5R,7S,8R,9R,10R,13S,14S,
16S,22S,23S) and 5 (5R,7S,8R,9R,10R,13S,14S,16S,22S).
Compounds 2ꢀ5 were evaluated in a panel of assays
(cancer cell cytotoxicity,14 antibiosis against pathogenic
bacteria and fungi,15 disruption of Candida biofilm
formation,16 and inhibition of planarian regeneration
and survival17). Only compound 3 exhibited weak activity
in the planaria assay (SI, Figure S5). At a concentration of
75 μM, ∼80% of the planarian segments did not regen-
erate, but instead disintegrated within 48 h. At 50 and 25
μM, no degeneration of the planarian fragments oc-
curred; however, the surviving body segments appeared
to regenerate more slowly, with the planaria exhibiting
sluggish swimming motions.
Figure 4. Calculated and experimental ECD data for 2 (A) and 3
(B) and VCD data for 2 (C) and 3 (D).
There are relatively few examples of the incorporation of
1 into natural products with 2ꢀ5 representing the first
examples of this scaffold being linked to a terpenoid
backbone. Although the compounds exhibited limited
biological activities, we find their novel structural features
highly valuable for adding a new element of chemical
diversification to our pure natural product library.
Two structurally related metabolites, teraspiridoles C
and D (4 and 5, respectively),13 were alsoobtainedfrom the
A. terreus extract. Compounds 4 and 5 were determined to
have molecular formulas consisting of C33H44N2O6 and
(13) Teraspiridole C (4): pale yellow solid; [R]24 þ62.8 (c 0.175,
D
CHCl3); UV (MeOH) λmax (log ε) 210 (4.34), 252 (4.01); IR (film) νmax
3346, 2978, 2929, 1710, 1604, 1482, 1391, 1293, 1244, 1183, 1145, 1064,
Acknowledgment. Research reported in this publication
was supported by the National Institute of General Med-
ical Sciences of the National Institutes of Health
RO1GM092219, a Challenge Grant from the Office of the
Vice President for Research, University of Oklahoma, and
an award through the Shimadzu Equipment Grant Program.
1014, 979, 756 cmꢀ1 13C and 1H NMR data, see Tables 1 and 2;
;
HRESIMS m/z 565.3276, [M
565.3278). Teraspiridole
þ
H]þ (calcd for C33H45N2O6,
D
(5): pale yellow solid; [R]24 þ14.4
D
(c 0.125, CHCl3); UV (MeOH) λmax (log ε) 210 (4.34), 252 (3.97); IR
(film) νmax 3345, 2982, 2926, 1722, 1605, 1477, 1373, 1305, 1293, 1245,
1155, 1145, 1065, 979, 756 cmꢀ1
;
13C and 1HþNMR data, see Tables 1 and
2; HRESIMS m/z 577.3272, [M þ H] (calcd for C34H45N2O6,
577.3278).
(14) Joyner, P. M.; Waters, A. L.; Williams, R. B.; Powell, D. R.;
Janakiram, N. B.; Rao, C. V.; Cichewicz, R. H. J. Nat. Prod. 2011,
74, 857–861.
(15) (a) Wang, X.; Filho, J. G. S.; Hoover, A. R.; King, J. B.; Ellis,
T. K.; Powell, D. R.; Cichewicz, R. H. J. Nat. Prod. 2010, 73, 942–948.
(b) Henrikson, J. C.; Ellis, T. K.; King, J. B.; Cichewicz, R. H. J. Nat.
Prod. 2011, 74, 1959–1964.
Supporting Information Available. NMR (1H and 13
C
NMR, HSQC, COSY, HMBC, and ROESY) and HRE-
SIMS data for compounds 2ꢀ5. Fungal identification
and associated data. This information is available free of
(16) Wang, X.; You, J.; King, J. B.; Powell, D. R.; Cichewicz, R. H.
J. Nat. Prod. 2012, 75, 707–715.
(17) Chan, J. D.; Marchant, J. S. J. Vis. Exp. 2011, 54, e3058.
The authors declare no competing financial interest.
D
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