Journal of Natural Products Val. 5 5 . No. 6. pp. 723-729.June I992
723
STUDIES ON ALOE, PART 10.' FEROXINS A AND B , TWO 0-GLUCOSYLATED 1-METHYLTETRALINSFROM CAPE ALOE GIOVANNASPERANW,~ PAOLOMANITTO, DIEGOMONTI, and DONATAPEZZUTO Dipartimento di Chimica Organica e Industriale, Uniwrsita di Milano and Centm di Studio sulle Sostanze Organicbe Naturali, CNR, via Venezian 21, 20133 Milano, Italy ABSTRACT.-TWO new 0-glucosylated 1-methyltetralins, feroxins A (21 and B 131, were isolated from a commercial sample of Cape aloe. Their structures and preferred conformations in solution were determined by spectroscopic methods and chemical transformations.
Aloe (or bitter aloes) is a natural drug well known since ancient times for its cathartic properties (2). It is the dried exudate from the cut leaves of Aloe species (Liliaceae) ( 3 ) . The latex of Aloe fwox Miller and hybrids of this species with Aloe afriana Miller and Aloe spicata Baker is known in commerce as Cape aloe (4). Although aloe is also used as a bittering agent in alcoholic beverages (5), its chemical composition is far from being completely known (3). The main constituents appear to belong to the structural families of 2-acetonyl-5-methylchromones(6), 1,8-dihydroxy-9-anthrones (7) or 1,8-dihydroxy-9,lO-anthraquinones(3). Recently, we reported the isolation and chemical characterization ofa new constituent of Cape aloe having the 1-methyltetralin skeleton, i.e., feroxidin (8); its absolute stereochemistry was proven to be 6S,8S,as in formula 1,by chemical correlaton (1). The present paper deals with the structural elucidation of two 0-glucosylated derivatives of 1 which we isolated from commercial Cape aloe and named feroxin A E27 and feroxin B [3].
1 X=H
2 X=
6,
ROHO
OH
R=H /OR
'For Part 9, see G. Speranza et al. (1).
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Wol. 55, No. 6
Journal of Natural Products RESULTS AND DISCUSSION
After addition of CHC13-hexane(10:3) to an Me2C0 extract of Cape aloe, a brown precipitate was formed. This insoluble material, when chromatographed on Si gel using gradient elution with CHCI, and EtOAc, gave crude feroxin A which was purified by preparative tlc. Similar flash chromatography of the mother liquor followed by dccc and semi-preparative hplc afforded feroxin B. Feroxin A {Z] was obtained from the drug in much smaller amounts than feroxin B. However, since feroxin A was shown to be identical in all respects with the product resulting from alkaline hydrolysis of feroxin B, we used feroxin B as a source of feroxin A. Feroxin A, C,,H240, (by elemental analysis and fabms), exhibited 'H- and 13C-nmr spectra (Tables 1 and 2) which appeared strongly reminiscent of those of feroxidin (8). Additional signals in the ranges 3 . 1 4 . 6 6 and 60-105 6 for 'H and I3C, respectively, suggested the presence of an 0-linked hexose residue, presumably a p-Dglucopyranosyl group (9,lO). This indication was strongly supported by a comparison with nmr data obtained for methyl P-D-glucopyranoside (Table 3). Definitive proof that feroxin A [Z] is a p-glucoside of feroxidin came from its enzymatic (&glucosidase) hydrolysis, giving the expected aglycone 1(1,8) and P-D-glucose. The linkage of the carbohydrate residue to the hydroxyl group in the 6 position TABLE1. 'H-nmr ( 3 0 0 MH
Assignments (6)of Feroxins A 121and B 131 in CD,OD at 25".' Compound
Proton
H-2 . . . . H-4 . . . . H,p-5 . . . . H,*-5 . . . . Ha-6 . . . . He-7 . . . . Ha-7 . . . . H,,-8 . . . . Me,4 . . . H-1' . . . . H-2' . . . . H-3' . . . . H-4' . . . . H-5' . . . . Ha-6' . . . Hb-6' . . . H-2" . . . . H-3" . . . . H-5". H-9" . H-6", H-8" . H-2"' . . . . H-3"' . . . . H-5"', H-9"' H-6"', H-8"'
... . . . . . . ... . . . . . . . . . . . . ...
. . . . . . .. . . ... . . . ,
,
. . . . .
. . . . . .
..
. . . ..... . ... .. . . . . . . . . ...... .. . . . . . . . . . ... ... .. .
..
. . . . . . . . .
... .. .. ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
.
. .
. .
.
. . . . .
..
. . . . . . . . . .
. . . . . . . . . . . . . . .
.. .. . .
2
3
6.10(d, 2.3); 6.03(d, 2.3) 3.09(ddd, 16.1,5.5, 1.6) 2.58(dd, 16.1, 10.2) 4 . 2 3 4 3 4 (m) 2.05(dm, 12.3) 1.78(ddd, 12.3, 12.1, 5.9) 3.14-3.22 (m)' 1.19(d, 7.0) 4.50(d, 7.9) 3.18(dd, 7.9,8.9) 3.38 (dd, 8.9) 3.28-3.33 Wd 3.28-3.33 (dd 3.87 (dd, 11.9, 1.7) 3.68(dd, 11.9, 5.1)
6.10(d, 2.3)b 6.04(d, 2.3)b 3.10(ddd, 16.0,6.2, 1.8) 2.61 (dd, 16.0, 10.3) 4.18-4.36(m) 2.05(dm, 11.6) 1.79(ddd, 11.6, 11.6,5.8) 3.18(ddq, 5.8, 1.6,6.9) 1.16(d, 6.9) 4.61 (d, 7.8) 3.34(dd, 7.8,9.3) 3.69(dd, 9.3,9.2) 4.96(dd, 9.2,9.6) 3.80-3.89 (m) 4.18-4.36 (m) 4.18-4.36(m) 6.24(d, 15.9) 7.57(d, 15.9) 7.29 (d, 8.7) 6.71 (d, 8.7) 6.37 (d, 15.9)' 7.67(d, 15.9) 7.45 (d, 8.7)' 6.79(d, 8.7)
'Splitting patterns and/ values (Hz) are given in parentheses; assignments were supported by homonuclear experiments; a = axial; e = equatorial; a' = pseudoawial; e' = pseudoequatorial. bsased on nOe experiments. See Figure 1. 'Obscured by the signal of H-2'. dBuried under the solvent signal. %elated by nOe enhancements. See text.
June 19921
Speranza et al.: 0-Glucosylated 1-Methyltetralins
725
TABLE2 . "C-nmr (75.47 MI+) Assignments (6)ofFerowinsAI2]andBI3] inCD. ODat 25O.' Compound
Carbon
c-1 c-2 c-3 c-4 C-4a c-5 C-6 c-7
. . . . . . .
C-8a 8-Me c-1' c-2' c-3' C-4' c-5' C-6' c-1" c-2" c-3" C-4" C.5". C.6. c-7" c - 1"' c-2" c-3" c-4"' C.5".
. . . .
. . . . . . . . . . . . . .
. . . . . . .
....... . . . . . . . . . . . . . . . . . . . . .
c-8 . . . . . . . . . . .
. . . .
. . . .
. . . .
. . . .
. . . .
. . . . . . . . . . . . . . . . . . . . .
.......
. . . . . . . . . . . . . .
. . . . . . . . . . . -9" . . -8" . . . . . .
. . . .
. . . .
. . . .
. . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . .
. . . .
. . . . -9" . c.6"'. -8'" . c-7'" . . . .
2
3
156.96b 101.46 156.86b 107.64 136.96 37.32 72.71 39.00 29.29 120.74 21.93 102.58 75.18 78.09 71.60 77.88 62.69
156.97b 101.55 156.85b 107.63 136.90 37.34 73.37 39.12 29.31 120.72 22.03 102.97 75.26 75.70 73.14 73.00 64.52 166.44' 114.74d 146.96' 127.00' 131. 17g 116.63h 161.21' 166.71' 114.84d 147.31' 127.11' 131.309 1 16.79h 161.39'
"Multidicities were obtained +om DEFT spectra. Assignments are based on *H-I3CCOSY and comparison with those of feroxidin [l)(8). of methyl (Ekp.coumarate. and of methyl p-Dglucopyranoside (Table 3). %ignals with the same superscript are interchangeable.
could then be inferred by n m r data . Glycosylation shifts fA8 = S(g1ycoside) . &aglycone) (8)] were found to be typical of a secondary alcoholic function flanked by two methylene groups(ll.17), i.e., inCD30DA6C-6 4-7.88, A8C-5 -3.07, A8C-7 -1.80, A8 Ha-6 +0.21, A8 He-5 +O . 18. A8 Ha..5 +O . 10. A8 He-7 +O . 17. A8 Ha-7 +O . 11. On the other hand. no significant differences (A8 O are defined as corresponding to a sterically hindered case I (13,14). An opposite conformational change occurs when one or two substituents are located at the p (pro-S) carbon of the aglycone moiety, and the corresponding rotamers (TH CO)are referred to as a sterically hindered case I1 (13,14). It has been found the p-D-glucosidation shifts (in pyridine-d5) are characteristic of each case and are of diagnostic value for determining the absolute configuration of secondary alcohols. H
4 FIGURE 2.
Schematized representation of a secondary alcohol p-mglucoside showing conventional symbols (for definitions, see text).
The negative A8 (C,) values are larger for the @-carbonanti to the pyranose-ring oxygen (pro-S carbon in 4 )than for the syn-carbon (pro-R) in alcohols corresponding to the sterically unhindered (S.U.) case or to the sterically hindered case I (S.H.I.). Opposite relationships are displayed by alcohols belonging to the sterically hindered case I1 (S.H.11) (13,14). In addition, typical AaS (C-1’) [defined as 6 (alcoholicglycoside) - 6 (methylglycoside)] were found to be - 2.6 1 2 1, -4.2 2 1, 0 2 1.5 ppm (in pyridined,) for P--glucosides of the S.U., S.H.1, or S.H.11 family, respectively (13,14).
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Journal of Natural Products
Wol. 55, No. 6
On the basis of the rules quoted above, the glucosidation shifts in feroxins in CD,OD [see above for A8 (C,) of feroxin A, and Tables 2 and 31 are consistent with the 6S configuration as shown by Speranza et al. (l),provided that these glucosides are referred to the S.U. (or S.H.1) case. In fact, given the structure of C, environment in the feroxins [-CH,-C,H(OR)CH,-1, no significant steric interactions are expected to occur between sugar and aglyconic moieties. Thus, a time-averaged conformation characterized by -90"
