solation and Total Synthesis of Stolonines A–C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera

.

Figure 1. Structures of stolonines A-C (1–3), 11-hydroxyascididemin (4) and cnemidine A (5) isolated from the tunicate C. stolonifera.

Table 1. NMR data for 1 in DMSO-d6 a.

Position	δC	δH (J in Hz)	gCOSY	gHMBCAD
1		12.20, br.s	2
2	138.5	8.82, d (3.0)	1	3, 3a, 7a
3	112.1
3a	126.2
4	121.3	8.22, dd (1.8, 7.2)	5	6, 7a
5	122.4	7.24, dt (1.8, 7.2)	4, 6	3a, 7
6	123.3	7.26, dt (1.8, 7.2)	5, 7	4, 7a
7	112.5	7.52, dd (1.8, 7.2)	6	3a, 5
7a	136.2
8	181.6
9	162.7
10		8.78, t (5.4)	11	9
11	35.5	3.50, dd (6.0, 6.6)	10, 12	9, 12
12	49.8	2.66, t (6.6)	11	11

a 1H NMR at 600 MHz referenced to residual DMSO solvent (δH 2.50 ppm) and 13C NMR at 150 MHz referenced to residual DMSO solvent (δC 39.52 ppm).

Stolonine A (1) was obtained as a white amorphous solid. The (−)-HRESIMS spectrum displayed a molecular ion [M−H]−at m/z 295.0390, which was consistent with the molecular formula C12H12N2O5S. The IR spectrum indicated the presence of an S=O stretching band at 1205 cm−1 [16]. A 1H NMR spectrum of 1 showed two exchangeable protons (δH 12.20 and 8.78 ppm), five aromatic protons (δH 8.82, 8.22, 7.52, 7.26 and 7.24 ppm) and two methylenes (δH 3.50 and 2.66 ppm). Further analysis of the 13C NMR and gHSQCAD spectra indicated that the molecule contained two carbonyls (δC 181.6 and 162.7 ppm), eight aromatic carbons (δC 138.5, 136.2, 126.2, 123.3, 122.4, 121.3, 112.5 and 112.1 ppm) and two methylenes (δC 49.8 and 35.5 ppm) (Table 1). J coupling constants of aromatic protons H-4 (δH 8.22, dd, 1.8, 7.2 Hz), H-5 (δH 7.24, dt, 1.8, 7.2 Hz), H-6 (δH 7.26, dt, 1.8, 7.2 Hz) and H-7 (δH 7.52, dd, 1.8, 7.2 Hz) and their COSY correlations were characteristic of a 1,2-disubstituted benzene ring (a, Figure 2). A gCOSY spectrum displayed correlations from the exchangeable proton H-1 (δH12.20, br.s) to H-2 (δH 8.82, d, 3.0 Hz) and also from H-11 (δH 3.50, dd, 6.0, 6.6 Hz) to the triplet exchangeable proton H-10 (δH 8.78, t, 5.4 Hz) and H-12 (δH 2.66, t, 6.6 Hz) facilitating the establishment of two other spin systems, –NH–CH= (b,Figure 2) and –NH–CH2–CH2– (c, Figure 2) respectively. The aromatic carbon C-3 (δC 112.1 ppm) was attached to C-2 (δC138.5 ppm) in the moiety b determined by a HMBC correlation from H-2 to C-3. A HMBC correlation from H-2 to C-7a (δC136.2 ppm) supported the linkage from a to b at C-7a (Figure 2). Both protons H-10 and H-11 in the moiety c showed HMBC correlations with a carbonyl carbon at δC 162.7 ppm suggesting the connection of this carbonyl to N-10 to form an amide bond (c, Figure 2). Two methylene signals at δH 3.50 and 2.66 ppm corresponding to carbons C-11 (δC 35.5 ppm) and C-12 (δC 49.8 ppm) as well as the relatively downfield resonance of the methylene C-12 were diagnostic of methylenes in a taurine moiety (c, Figure 2) [17,18,19].

Table 1. NMR data for 1 in DMSO-d6 a.

Figure 2. Partial structures (a, b and c) of 1 and their key HMBC correlations.

Figure 2. Partial structures (a, b and c) of 1 and their key HMBC correlations.

No HMBC correlation from any proton to the carbonyl C-8 (δC 181.6 ppm) was observed when HMBC experiments were performed and optimized with different JHC couplings. Therefore, two different isomers 1-I and 1-II were conceivable from these data (Figure 3). Detailed HMBC analysis showed that H-2 had a HMBC correlation with C-3a (δC 126.2 ppm). This suggested that 1 was favorable to 1-I since the H-2 to C-3a correlation in 1-I was a three-bond coupling while the H-2 to C-3a correlation in 1-II was a four-bond coupling (Figure 3).

Figure 3. Two possible structures 1-I and 1-II of 1 (1-I and 1-II are possible structural isomers of 1).

Figure 3. Two possible structures 1-I and 1-II of 1 (1-I and 1-II are possible structural isomers of 1).

Table 2. Comparison of experimental and calculated 13C and 1H chemical shifts for 1 in DMSO-d6.

Position	δC (Exp.)	1-I		1-II		δH (Exp.)	1-I		1-II
		δC (Calc.)	δC (Scaled)	δC (Calc.)	δC (Scaled)		δH (Calc.)	δH (Scaled)	δH (Calc.)	δH (Scaled)
2	138.5	136.9	140.3	141.3	142.8	8.82	8.74	8.61	8.84	8.67
3	112.1	111.5	112.9	111.2	110.2
3a	126.2	124.1	126.5	123.0	122.9
4	121.3	118.9	120.9	124.3	124.4	8.22	8.62	8.48	8.40	8.19
5	122.4	120.1	122.1	121.1	120.9	7.24	7.63	7.40	7.63	7.35
6	123.3	120.9	123.0	129.4	129.9	7.26	7.59	7.36	8.00	7.76
7	112.5	108.7	109.9	114.8	114.1	7.52	7.55	7.31	7.53	7.24
7a	136.2	131.9	134.9	134.4	135.3
8	181.6	176.7	183.2	172.5	176.5
9	162.7	156.8	161.7	159.4	162.4
11	35.5	37.1	32.6	36.9	29.8	3.50	3.69	3.11	3.71	3.08
12	49.8	57.2	54.4	58.4	53.1	2.66	3.55	2.95	3.57	2.93
CMAE			1.5		3.1			0.23		0.25
DP4		100.0%		0.0%			85.3%		14.7%

Stolonine A (1): white, amorphous solid; UV (MeOH) λmax (log ε) 210 (3.8), 252 (3.5) and 325 (3.3) nm; IR (film) νmax 3307, 1681, 1205, 1049 and 802 cm−1; 1H (600 MHz, DMSO-d6) and 13C (150 MHz, DMSO-d6) NMR data are summarized in Table 1; (−)-HRESIMS m/z 295.0390 [M − H]− (calcd for [C12H11N2O5S]−, 295.0394, Δ −1.4 ppm).

Mar. Drugs 2015, 13(7), 4556-4575; doi:10.3390/md13074556

Article

Isolation and Total Synthesis of Stolonines A–C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera

Trong D. Tran 1, Ngoc B. Pham 1, Merrick Ekins 2, John N. A. Hooper 1,2 and Ronald J. Quinn 1,*

1

Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland 4111, Australia

2

Queensland Museum, Brisbane, Queensland 4101, Australia

*

Author to whom correspondence should be addressed; Tel.: +61-7-3735-6009; Fax: +61-7-3735-6001.

http://www.mdpi.com/1660-3397/13/7/4556/htm
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RAIN FOREST, KODIAK ISLAND, ALASKA, USA
 

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ON-SITE EXPERIENCES INCLUDE INTERACTING WITH A
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I HOPE YOU HAVE ENJOYED YOUR VIST TO
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RAINFOREST VEGETATION

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Taurine

.

2-aminoethanesulfonic acid

C2 H7 N O3 S

TAURINE

This is an H-NMR of Taurine depicting all peaks.


This is a magnified view of the H-NMR of Taurine. This is a set of two triplet of peaks at 3.38 to 3.42 ppm which corresponds to the “Ha” protons attached to the carbon at the “1” position and at 3.23 to 3.28 ppm which corresponds to the “Hb” protons attached to the carbon at the “2” position. These peaks correspond to the sp3 hybridized hydrogen atoms bonded to the first and second carbon in the compound. There is splitting of the signal in the form of three peaks as the hydrogens are affected by two equavalent adjacent protons present bonded to the first and second carbon; from the N+1 rule, N would then equal 2 for each proton, so N+1, (2+1 = 3), 3 peaks would be observed. The three peaks corresponding to “Ha” deshielded by the electron-withdrawing group SO3H, as well causing a chemical shift to the left. This is so because normally without deshielding an sp3 hydrogen attached to a carbon is around 1.4 ppm. For “Hb” is deshielded by an amine group, which is less electronegative, and therefore less electron withdrawing than the effect seen on “Ha” so it is moved to the left less. The triplet peaks exhibit similar heights because the height of peaks corresponds to the ratio of protons between carbons; since both carbons have two H’s, the ratio is 1:1, so their heights are similar.





This is the C-NMR spectra of Taurine depicting all peaks.


This is a magnified view of the C-NMR of Taurine. It depicts a single peak from 50.1-50.23ppm and corresponding to the first carbon bonded to both the sulfur as well as the second carbon. The reason why the C-NMR would correspond to 50.1-50.23 is because the H-NMR corresponding to the protons attached to Carbon #1 is around 3.4 ppm. Since C-NMR peaks represent 15-20 times the amount of ppm of the protons attached to it, 3.4 x 15 is approximately 51 ppm. (See above explanation for H-NMR peak at 3.4 ppm)



This is a magnified view of the C-NMR of Taurine. There is a single peak at approximately 38.20 ppm, which corresponds to the second carbon bonded to the nitrogen group. The reason why the C-NMR would correspond to 38.2 is because the H-NMR corresponding to the protons attached to Carbon #2 is around 3.2 ppm. Since C-NMR peaks represent approximately 15-20 times the amount of ppm of the protons attached to it, 3.2 x 15 is approximately 48 ppm. (See above explanation for H-NMR peak at 3.2 ppm). Although the peak doesn’t exactly match with the H-NMR prediction, it can be deduced that this C-NMR peak correlates with Carbon #2 because it is the lesser ppm of the two C-NMR peaks.

2D [1H,1H]-TOCSY

1D DEPT90

1D DEPT135

2D [1H,13C]-HSQC

2D [1H,13C]-HMBC

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MT. MC KINLEY, DENALI, ALASKA, USA

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Denali /dᵻˈnɑːli/ is the highest mountain peak in North America, with a summit elevation of 20,310 feet above sea level. At some 18,000 ft, the base-to-peak rise is the largest of any mountain situated entirely above sea level. Wikipedia

HI EVERYONE. YESTERDAY, WE WERE AT THE GATEWAY ARCH IN
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