Document

Supporting Information
Antileishmanial Metabolites from
Geosmithia langdonii
Lourin G. Malak,†,‡ Mohamed Ali Ibrahim,†,§ Daoud W. Bishay,‡ Afaf M. Abdelbaky,‡ Ahmed M. Moharram, Babu Tekwani,† Stephen J. Cutler,║ and Samir A.
Ross†,,*
†National
Center for Natural Products Research, School of Pharmacy, The University
of Mississippi, University, MS 38677, USA
‡Pharmacognosy Department, Faculty of Pharmacy, Assiut University, Assiut 71526,
Egypt
§Department of Chemistry of Natural Compounds, National Research Center, Dokki
12622, Cairo, Egypt
 Assiut University Mycological Center, Assiut University, Assiut 71515, Egypt
║Medicinal Chemistry Department, School of Pharmacy, University of Mississippi,
University, MS 38677, USA
Pharmacognosy Department, School of Pharmacy, University of Mississippi,
University, MS 38677, USA
Table of contents:
Fig.
Title
Page
SI 1
1H
NMR spectrum of 4-(2`,4`-dihydroxy-6`-(hydroxymethyl)benzyl)
benzene-1,2-diol (1) [400 MHz, CD3OD]
5
SI 2
13C
NMR spectrum of 4-(2`,4`-dihydroxy-6`-(hydroxymethyl) benzyl)
benzene-1,2-diol (1) [100 MHz, CD3OD]
6
SI 3
DEPT spectrum of 4-(2`,4`-dihydroxy-6`- (hydroxymethyl) benzyl)
benzene-1,2-diol (1) [CD3OD]
7
SI 4
HMQC spectrum of 4-(2`,4`-dihydroxy-6`-(hydroxymethyl) benzyl)
benzene-1,2-diol (1) [CD3OD]
8
SI 5
HMBC spectrum of 4-(2`,4`-dihydroxy-6`-(hydroxymethyl) benzyl)
benzene-1,2-diol (1) [CD3OD]
9
SI 6
1H
SI 7
13C
NMR spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`-methylsalicyloxy)
-2-methyl-2-cyclohexen-1-one (2) [100 MHz, pyridine-d5]
11
SI 8
DEPT spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`-methylsalicyloxy) -2methyl-2-cyclohexen-1-one (2) [pyridine-d5]
12
SI 9
HMQC spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`-methylsalicyloxy) - 13
2-methyl-2-cyclohexen-1-one (2) [pyridine-d5]
NMR spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`-methylsalicyloxy) - 10
2-methyl-2-cyclohexen-1-one (2) [400 MHz, pyridine-d5]
Fig.
Title
Page
SI 10
HMBC spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`-methylsalicyloxy) -2- 14
methyl-2-cyclohexen-1-one (2) [pyridine-d5]
SI 11
Reaction of compound 2 with either (R)- or (S)-MTPA
15-18
SI 12
NOESY spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`-methylsalicyloxy) 2-methyl-2-cyclohexen-1-one (2) [400 MHz, pyridine]
19
SI 13
1H
20
SI 14
13C
SI 15
Reaction of compound 3 with either (R)- or (S)-MTPA
22-25
SI 16
1H
26
SI 17
13C
SI 18
NMR spectrum (+)-epiepoformin (3) [400 MHz, CDCl3]
NMR spectrum of (+)-epiepoformin (3) [100 MHz, CDCl3]
NMR spectrum of (-) dihydroepiepoformin (4) [400 MHz, CDCl3]
21
NMR spectrum of (-) dihydroepiepoformin (4) [100 MHz, CDCl3]
27
1H
NMR spectrum of (4S,5S)-4,5-dihydroxy-2-methyl-cyclohex-2-enone
(5) [400 MHz, CD3OD]
28
SI 19
13C
NMR spectrum of (4S,5S)-4,5-dihydroxy-2-methyl-cyclohex-2-enone
(5) [100 MHz, CD3OD]
29
SI 20
1H
30
SI 21
13C
NMR spectrum of 6-methylsalicylic acid
(6) [400 MHz, pyridine-d5]
NMR spectrum of 6-methylsalicylic acid (6) [100 MHz, pyridine-d5]
31
Fig.
Title
Page
SI 22
1H
SI 23
13C
SI 24
1H
SI 25
13C
SI 26
1H
NMR spectrum of 2,5-dihydroxy-benzaldehyde (9) [400 MHz,
CD3OD]
36
SI 27
13C
37
SI 28
13C
NMR spectrum of 2,5-dihydroxy-benzaldehyde (9) [100 MHz,
CD3OD]
38
SI 29
1H
39
SI 30
13C
SI 31
1H
NMR spectrum of 2,5-dihydroxybenzyl alcohol (11) [400 MHz,
CD3OD]
41
SI 32
13C
42
SI 33
1H
43
SI 34
13C
SI35
Selected HMBC correlations for compounds 1 and 2
NMR spectrum of gentisylquinone (7) [400 MHz, CDCl3]
32
NMR spectrum of gentisylquinone (7) [100 MHz, CDCl3]
33
NMR spectrum of 3,4-dihydroxytoluene (8) [400 MHz, CD3OD]
34
NMR spectrum of 3,4-dihydroxytoluene (8) [100 MHz, CD3OD]
NMR spectrum of 2,5-dihydroxy-benzaldehyde (9) [100 MHz, CDCl3]
NMR spectrum of 3-hydroxybenzyl alcohol (10) [400 MHz, CD3OD]
NMR spectrum of 3-hydroxybenzyl alcohol (10) [100 MHz, CD3OD]
NMR spectrum of 2,5-dihydroxybenzyl alcohol (11)
[100 MHz, CD3OD]
NMR spectrum of 3-hydroxytoluene (12) [400 MHz, pyridine-d5]
NMR spectrum of 3-hydroxytoluene (12) [100 MHz, pyridine-d5]
35
40
44
45
SI 1: 1H NMR spectrum of 4-(2`,4`-dihydroxy-6`-(hydroxymethyl) benzyl)
benzene-1,2-diol (1) [400 MHz, CD3OD]
SI 2: 13C NMR spectrum of 4-(2`,4`-dihydroxy-6`-(hydroxymethyl)
benzyl) benzene-1,2-diol (1) [100 MHz, CD3OD]
SI 3: DEPT spectrum of 4-(2`,4`-dihydroxy-6`- (hydroxymethyl) benzyl)
benzene-1,2-diol (1) [CD3OD]
SI 4: HMQC spectrum of 4-(2`,4`-dihydroxy-6`(hydroxymethyl)benzyl)benzene-1,2-diol (1) [CD3OD]
SI 5: HMBC spectrum of 4-(2`,4`-dihydroxy-6`-(hydroxymethyl) benzyl)
benzene-1,2-diol (1) [CD3OD]
SI 6: 1H NMR spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`methylsalicyloxy) -2-methyl-2-cyclohexen-1-one (2) [400 MHz, pyridine-d5]
SI 7: 13C NMR spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`methylsalicyloxy) -2-methyl-2-cyclohexen-1-one (2) [100 MHz, pyridine-d5]
SI 8: DEPT spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`-methylsalicyloxy)
-2-methyl-2-cyclohexen-1-one (2) [pyridine-d5]
SI 9: HMQC spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`-methylsalicyloxy)
-2-methyl-2-cyclohexen-1-one (2) [pyridine-d5]
SI 10: HMBC spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`methylsalicyloxy) -2-methyl-2-cyclohexen-1-one (2) [pyridine-d5]
SI 11: Reaction of compound 2 with either (R)- or (S)-MTPA
Mosher esters formation of compound 2
Compound 2 + R-MTAP
H-3
H-6
H-5
H-4
H-4
Compound 2 + S-MTAP
Final Structure
(4R, 5R, 6R)-4,5-dihydroxy-6-(6`-methylsalicyloxy) -2-methyl-2-cyclohexen-1-one
Final Structure Based on
NOE
SI 12: NOESY spectrum of (4R, 5R, 6R)-4,5-dihydroxy-6-(6`methylsalicyloxy) -2-methyl-2-cyclohexen-1-one (2) [pyridine-d5]
SI 13: 1H NMR spectrum (+)-epiepoformin (3) [400 MHz, CDCl3]
SI 14: 13C NMR spectrum of (+)-epiepoformin (3) [100 MHz, CDCl3]
SI 15: Reaction of compound 3 with either (R)- or (S)-MTPA
Mosher esters formation of compound 3
Compound 3 + SMTPA / Pyridine-d5
Compound 3 + RMTPA / Pyridine-d5
Compound 3 /
Pyridine-d5
Compound 3 + SMTPA / Pyridine-d5
Compound 3 + RMTPA / Pyridine-d5
Final Structure of Compound 3
SI 16: 1H NMR spectrum of (-) dihydroepiepoformin (4) [400 MHz, CDCl3]
SI 17: 13C NMR spectrum of (-) dihydroepiepoformin (4) [100 MHz, CDCl3]
SI 18: 1H NMR spectrum of (4S,5S)-4,5-dihydroxy-2-methyl-cyclohex-2enone (5) [400 MHz, CD3OD]
SI 19: 13C NMR spectrum of (4S,5S)-4,5-dihydroxy-2-methyl-cyclohex-2enone (5) [100 MHz, CD3OD]
SI 20: 1H NMR spectrum of 6-methylsalicylic acid (6)
[400 MHz, pyridine-d5]
SI 21: 13C NMR spectrum of 6-methylsalicylic acid (6)
[100 MHz, pyridine-d5]
SI 22: 1H NMR spectrum of gentisylquinone (7)
[400 MHz, CDCl3]
SI 23: 13C NMR spectrum of gentisylquinone (7)
[100 MHz, CDCl3]
SI 24: 1H NMR spectrum of 3,4-dihydroxytoluene (8)
[400 MHz, CD3OD]
SI 25: 13C NMR spectrum of 3,4-dihydroxytoluene (8)
[100 MHz, CD3OD]
SI 246: 1H NMR spectrum of 2,5-dihydroxy-benzaldehyde (9)
[400 MHz, CD3OD]
SI 27: 13C NMR spectrum of 2,5-dihydroxy-benzaldehyde (9)
[100 MHz, CDCl3]
SI 28: 13C NMR spectrum of 2,5-dihydroxy-benzaldehyde (9)
[100 MHz, CD3OD]
SI 29: 1H NMR spectrum of 3-hydroxybenzyl alcohol (10)
[400 MHz, CD3OD]
SI 30: 13C NMR spectrum of 3-hydroxybenzyl alcohol (10)
[100 MHz, CD3OD]
SI 31: 1H NMR spectrum of 2,5-dihydroxybenzyl alcohol (11)
[400 MHz, CD3OD]
SI 32: 13C NMR spectrum of 2,5-dihydroxybenzyl alcohol (11)
[100 MHz, CD3OD]
SI 33: 1H NMR spectrum of 3-hydroxytoluene (12)
[400 MHz, pyridine-d5]
x
SI 34: 13C NMR spectrum of 3-hydroxytoluene (12)
[100 MHz, pyridine-d5]
SI 35: Selected HMBC correlations for compounds 1 and 2