Hyrtioerectine D, E F

Hyrtioerectine D, E F


Figure 1. Structures of hyrtioerectines D–F (1–3) isolated from the marine sponge Hyrtios species.

Figure 2. COSY and HMBC correlations observed for compound 1.

Structure Elucidation of Compounds 1–3

The HRMS of compound 1 established a molecular formula C₂₀H₁₃N₃O₄ requiring 16 degrees of unsaturation. Compound 1 gave a bluish color on the TLC with FeCl₃ indicating its phenolic nature. Its ¹H NMR spectrum (in methanol-d₄, Table 1) showed resonances for eight aromatic protons ranging from 6.80 to 9.64 ppm, suggesting the absence of any aliphatic moiety in the molecule. The ¹³C NMR spectrum of 1 (Table 1) displayed resonances for 20 carbons including 8 methines and 12 quaternary carbons. Two of the ¹³C quaternary resonances were deshielded at δ 154.3 (C-6) and 153.0 (C-6′) suggesting the oxygenation of their corresponding carbons. Interpretation of the 1D (¹H and ¹³C) and 2D (¹H–¹H COSY, HSQC and HMBC) NMR spectroscopic data supported the presence of two ABX systems for trisubstituted β-carboline (H-5, H-7 and H-8) and disubstituted indole (H-4ʹ, H-5ʹ and H-7ʹ) moieties, respectively. These two moieties include 15 degrees of unsatuartion suggesting the need for an additional degree of unsaturation in 1. Interpretation of the NMR data (¹H, COSY and HSQC) supported the 3,4,6-trisubstitution of the β-carboline moiety. This was evident from the resonating signals at δ 8.07 (1H, d, J = 2.0, H-5), 6.80 (1H, dd, J = 8.5, 2.0, H-7), 7.30 (1H, d, J = 8.5, H-8) and 9.64 (s, H-1). Additional signals at δ 8.87 (1H, s, H-2ʹ), 7.57 (1H, d, J = 8.7, H-4ʹ), 7.13 (1H, dd, J = 8.7, 2.3, H-5ʹ) and 7.60 (1H, d, J = 2.3, H-7ʹ) were assigned as 3,6-disubstituted indole moiety. The HSQC experiment allowed the unambiguous assignment of the protonated methine carbons in 1 (Table 1). The quaternary carbons were unambiguously assigned from HMBC data (Table 2 and Figure 2). For example, the location of the OH moieties at C-6 and C-6′ was supported from HMBC correlations of H-5/C-6, H-7/C-6, H-8/C-6 and H-4′/C-6′, H-5′/C-6′ and H-7′/C-6′ (Table 2). The connection of the indole and β-carboline moieties through C-3 and C-3ʹ was supported from a ³J_CH HMBC cross peak between H-2ʹ of the indole moiety (δ 8.87) and C-3 of the β-carboline moiety (δ 138.1). Finally, the quaternary carbon resonating at δ 173.0 (C-8′) was assigned as a carboxylic moiety at C-4 completing the degrees of unsaturation in 1. This was supported by an IR band at 1725 cm⁻¹ for the carbonyl moiety of the carboxylic acid. Furthermore, the MS fragment ion at m/z 315.1009 with the molecular formula C₁₉H₁₃N₃O₂ [M − COOH + H]⁺ supported the presence of the carboxylic functionality, thus completing the assignment of 1.
Compound 2displayed a pseudomolecular ion peak at m/z 374.1138 corresponding to C₂₁H₁₆N₃O₄ [M + H]⁺, being 14 mass unit (CH₂) more than 1 and requiring 16 degrees of unsaturation. Comparison of the NMR data of 2 with those of 1 showed identical similarity of the ¹H and ¹³C NMR resonances of both compounds (Table 1). Moreover, a new three-proton singlet in ¹H NMR at δ 3.84 (H₃-9ʹ) correlates in the HSQC with the ¹³C NMR signal at δ 55.8 (C-9ʹ) suggesting the presence of a methoxyl moiety in 2 at C-6. The assignment of the methoxyl moiety at C-6 was secured from HMBC cross peak of OCH₃/C-6 (Table 2). Additionally, the unambiguous assignments of the protonated and quaternary carbons in 2 were secured from HSQC and HMBC experiments, respectively, thus completing the assignment of 2.


Hyrtioerectine D (1): yellow solid; UV (MeOH) λ_max (log ε) 387 nm (3.85), 248 nm (3.85), 312 nm (4.05); IR ν_max (film) 3600, 3500, 3020, 2980, 1725, 1610, 1405, 1290, 1255, 1220, 890 cm⁻¹; NMR data, see Table 1, Table 2; positive HRESIMS m/z 360.0981 (calcd for C₂₀H₁₄N₃O₄ [M + H]⁺, 360.0984).
Hyrtioerectine E (2): yellow solid; UV (MeOH) λ_max (log ε) 420 nm (3.90), 252 nm (3.95), 315 nm (4.15); IR ν_max (film) 3595, 3545, 3015, 2980, 1720, 1612, 1410, 1290, 1250, 1220, 895 cm⁻¹; NMR data, see Table 1, Table 2; positive HRESIMS m/z 374.1138 (calcd for C₂₁H₁₆N₃O₄ [M + H]⁺, 374.1140).
Hyrtioerectine F (3): yellow solid; UV (MeOH) λ_max (log ε) 380 nm (3.95), 240 nm (4.10), 315 nm (4.00); IR ν_max (film) 3590, 3500, 3350, 3010, 2985, 1655, 1615, 1405, 1290, 1255, 1215, 895 cm⁻¹; NMR data, see Table 1, Table 2; positive HRESIMS m/z 359.1142 (calcd for C₂₀H₁₅N₄O₃ [M + H]⁺, 359.1144).

Table 1. NMR spectroscopic data for hyrtioerectines D–F (1–3) (in methanol-d₄).

	Hyrtioerectine D		Hyrtioerectine E		Hyrtioerectine F
Position	δC (mult.) a	δH, mult. (J in Hz)	δC (mult.) a	δH, mult. (J in Hz)	δC (mult.) a	δH, mult. (J in Hz)
1	140.8 (CH)	9.64, s	141.2 (CH)	9.66, s	139.6 (CH)	9.71, s
3	138.1 (qC)		138.2 (qC)		138.3 (qC)
4	138.8 (qC)		138.8 (qC)		138.8 (qC)
4a	115.9 (qC)		115.8 (qC)		115.9 (qC)
4b	130.1 (qC)		130.3 (qC)		130.4 (qC)
5	108.2 (CH)	8.07, d (2.0)	110.1 (CH)	8.10, d (2.2)	107.2 (CH)	8.09, d (2.2)
6	154.3 (qC)		156.2 (qC)		154.2 (qC)
7	113.5 (CH)	6.80, dd (8.5, 2.0)	113.5 (CH)	6.78, dd (8.5, 2.2)	113.7 (CH)	6.76, dd (8.5, 2.2)
8	113.1 (CH)	7.30, d (8.5)	113.1 (CH)	7.27, d (8.5)	113.5 (CH)	7.32, d (8.5)
8a	132.1 (qC)		132.2 (qC)		132.4 (qC)
9a	133.2 (qC)		133.1 (qC)		133.2 (qC)
2′	119.6 (CH)	8.87, s	119.5 (CH)	8.88, s	119.6 (CH)	8.87, s
3′	123.2 (qC)		123.2 (qC)		123.2 (qC)
3a′	137.5 (qC)		137.5 (qC)		137.5 (qC)
4′	114.1 (CH)	7.57, d (8.7)	114.1 (CH)	7.61, d (8.7)	114.1 (CH)	7.64, d (8.0)
5′	119.7 (CH)	7.13, dd (8.7, 2.3)	119.6 (CH)	7.15, dd (8.7, 2.2)	119.7 (CH)	7.17, dd (8.7, 2.0)
6′	153.0 (qC)		153.1 (qC)		153.0 (qC)
7′	106.7 (CH)	7.60, d (2.3)	106.9(CH)	7.62, d (2.2)	106.7 (CH)	7.65, d (2.0)
7a′	132.6 (qC)		132.5 (qC)		132.6 (qC)
8′	173.0 (qC)		173.0 (qC)		164.2 (qC)
9′			55.8 (CH3)	3.84, s

^a multiplicities of the signals were obtained from HSQC experiments; qC = quaternary carbon, CH = methine; CH₃ = methyl.

Table 2. Selected HMBC correlations for hyrtioerectines D–F (1–3) (in methanol-d₄).

C#	Hyrtiooerectine D (1)	Hyrtioerectine E (2)	Hyrtioerectine F (3)
	HMBC (H→C#)	HMBC (H→C#)	HMBC (H→C#)
3	H-1, H-2′	H-1, H-2′	H-1, H-2′
4	-	-	-
4a	H-1, H-5	H-1	H-1, H-5
4b	H-8	H-8	H-8
5	H-7	H-7	H-7
6	H-5, H-7, H-8	H-5, H-7, H-8, H3-9′	H-5, H-8
7	H-5	H-5	H-5
8	H-7	H-7	H-7
8a	H-5, H-7	H-5, H-7	H-5, H-7
9a	H-1	H-1	H-1
2′	-	-	-
3′	H-2′	H-2′	H-2′
3a′	H-2′, H-4′, H-5′, H-7′	H-2′, H-4′, H-7′	H-2′, H-4′, H-7′
4′	H-5′	H-5′	H-5′
5′	H-4′, H-7′	H-4′, H-7′	H-4′, H-7′
6′	H-4′, H-5′, H-7′	H-4′, H-5′, H-7′	H-4′, H-5′, H-7′
7′	H-5′	H-5′	H-5′
7a′	H-2′, H-4′, H-7′	H-2′, H-4′, H-7′	H-2′, H-4′, H-7′

see
 http://www.mdpi.com/1660-3397/11/4/1061/htm

Mar. Drugs 2013, 11(4), 1061-1070; doi:10.3390/md11041061

Article

Bioactive Compounds from the Red Sea Marine Sponge Hyrtios Species

Diaa T. A. Youssef ^1,*, Lamiaa A. Shaala ² and Hani Z. Asfour ³

¹

Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia

²

Natural Products Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia

³

Department of Medical Parasitology, Faculty of Medicine, Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia

*Author to whom correspondence should be addressed; Tel.: +966-548-535-344; Fax: +966-269-516-96.

 Suez Canal University, Egypt

Suez Canal University  

University in Ismaïlia, Egypt

The Suez Canal University is an Egyptian university serving the Suez Canal area, having its faculties divided among the Suez Canal governorates. It was established in 1964. It is notable for its non-classic research. Wikipedia

Address: EL SALAM DISTRICT، ISMAILEYA، Egypt

 

 

 

 

 
 

 ISMAILEYA، Egypt
 

 

 

 
 

 

 

 
 
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Terretrione D

.

Terretrione D
Key COSY and HMBC correlations of 2.


 

Figure 1. Structures of Compounds 1–6.

methyl-2-([2-(1H-indol-3-yl)ethyl]carbamoyl)acetate (1),
Terretrione D (2)
tryptamine (3),
indole-3-carbaldehyde (4),
3,6-diisobutylpyrazin-2(1H)-one (5) and
terretrione C (6),

Table 1. NMR data of Compound 2 (CD₃OD, 600 and 150 MHz).

Position	δC, Type a	δH, m (J in Hz)	HMBC	NOESY
2	173.0, C b
3	60.1, CH	4.18, d (4.8)	C-2, C-5, C-1′	H-6, H3-8, H-1′
5	173.2, C
6	56.4, CH	4.68, dd (8.4, 6.6)	C-5, C-7, C-1″	H-3, H3-8, H2-1″
7	173.1, C b
8	22.9, CH3	1.90, s	C-2, C-7
1′	32.2, CH	2.07, m	C-2, C-3, C-2′, C-3′	H-3
2′	19.8, CH3	0.81, d (7.2)	C-1′, C-3
3′	18.2, CH3	0.78, d (7.2)	C-1′, C-3
1″	39.0, CH2	3.11, dd (13.8, 6.6) 2.88, dd (13.8, 8.4)	C-2″, C-3″, C-6, C-7	H-6
2″	138.6, C
3″	130.2, CH	7.23, m	C-2″, C-5″
4″	129.4, CH	7.24, m	C-2″
5″	127.7, CH	7.14, m	C-3″, C-7″
6″	129.4, CH	7.24, m	C-2″
7″	130.2, CH	7.23, m	C-1″, C-5″

^a Multiplicities were deduced by DEPT and HSQC; ^b signals may be interchangeable.

  
compound 2 (Figure 1) showed a molecular formula C₁₆H₂₀N₂O₃, as deduced from the HRESIMS pseudomolecular ion peak at m/z 289.1555 [M + H]⁺, requiring eight degrees of unsaturation. The ¹³C NMR spectrum revealed signals for 16 carbons. Careful investigation of the ¹H, ¹³C and 2D NMR spectra supported the presence of a valine residue in 2. This was evident from the NMR signals at δ_H/δ_C 0.81 (3H, d, J = 7.2 Hz, H₃-2′)/19.8 (C-2′), 0.78 (3H, d, J = 7.2 Hz, H₃-3′)/18.2 (C-3′), 2.07 (1H, m, H-1′)/32.2 (C-1′), 4.18 (1H, d, J = 4.8 Hz, H-3)/60.1 (C-3) and δ_C 173.0 (C-2). In addition, signals for a 2-benzylmalonamide moiety were observed. The signals at δ_C 138.6 (C-2″), δ_H/δ_C 7.23 (2H, m)/130.2 (C-3″,7″), 7.24 (2H, m)/129.4 (C-4″,6″) and 7.14 (1H, m)/127.7 (C-5″) supported the existence of a phenyl group. In addition, the coupled signals at δ_H 3.11 (1H, dd, J = 13.8, 6.6 Hz, H-1″a) and 2.88 (1H, dd, J = 13.8, 8.4 Hz, H-1″b) showed vicinal coupling to the signal at δ_H 4.68 (1H, dd, J = 8.4, 6.6 Hz, H-6) in the ¹H,¹H-COSY spectrum. Furthermore, the two amidic carbonyls (C-5 and C-7) of the 2-benzylmalonamide moiety resonate at δ_C 173.2 and 173.1. Finally, a three-proton singlet at δ_H 1.90, which correlates with the ¹³C signal at δ_C 22.9, was assigned to a methyl group linked to N-1. The linkage of the valine residue with the 2-benzylmalonamide moiety through N-1 and N-4 was supported by the HMBC correlations of H-3/C-5, H-3/C-2, H₃-8/C-2 (δ_C 173.0) and H₃-8/C-7 (δ_C 173.1). The HMBC correlations of H₃-8 to C-2 and C-7 secured the placement of the N-methyl at N-1. Additional HMBC correlations within the valine and the 2-benzylmalonamide moieties (Table 1 and Figure 2) confirmed the assignment of all carbon signals and completing the flat structure of 2. The absolute configuration of the chiral center at C-3 of the valine residue was established by analysis of the degradation product of 2. A small amount of 2 was hydrolyzed with 6N HCl to give valine residue, which was analyzed by chiral HPLC, and its retention time was compared with the retention times of authentic standards (d- and l-valine). The amino acid in 2 was determined as l-valine. In addition, the relative configuration of C-6 was determined as 6S*, since the NOESY spectrum (Table 1) exhibited a strong correlation between H-3 (δ_H 4.18) and H-6 (δ_H 4.68). The MM2 ChemBio3D Ultra 14.0 (ChemBioOffice^® Ultra 14.0) energy minimized drawing for Compound 2 was also created and supports a significant NOESY correlation between H-3 and H-6 (Figure 3). Therefore, 2 was assigned as (3S,6S)-6-benzyl-3-isopropyl-1-methyl-1,4-diazepane-2,5,7-trione and named terretrione D. Terretrione D possesses the 1,4-diazepane skeleton, which was previously reported in terretriones A–C. These compounds were reported from the marine fungus Aspergillus terreus [18]. It is worth mentioning that terretrione D is 4-demethylterretrione B, and the NMR data of 2 are comparable with those of terretrione B [18]. Compound 2 is reported here for the first time from a natural source, and therefore, it is considered as a new natural product.
The known compounds were identified by extensive study of their spectral data, including HRESIMS, 1D and 2D NMR data, as well as by comparison with the available data in the literature. Thus, the compounds were identified as methyl-2-([2-(1H-indol-3-yl)ethyl]carbamoyl)acetate (1) [16], tryptamine (3), indole-3-carbaldehyde (4), 3,6-diisobutylpyrazin-2(1H)-one (5) [17] and terretrione C (6) [18]. The amino acid residue of compound 6 was also determined as N-methyl-l-isoleucine by HPLC chiral analysis of the hydrolysate of 6 (see Section 3.6). Furthermore, the relative configuration of its C-6 was assigned as 6S* by the NOESY correlation, similar to that described for 2.



Terretrione D (2): White amorphous powder; [α]_D −65.7 (c 1.5, MeOH); UV (MeOH) λ_max (log ε) 314 (2.65) nm; IR ν_max (film) 3367, 1682, 1630, 1540, 1455, 1288, 1094, 702 cm⁻¹; NMR data, see Table 1; HRESIMS m/z 289.1555 (calcd. for C₁₆H₂₁N₂O₃, [M + H]⁺, 289.1552).
 see
 http://www.mdpi.com/1660-3397/13/4/1698

Mar. Drugs 2015, 13(4), 1698-1709; doi:10.3390/md13041698

Article

Identification and Bioactivity of Compounds from the Fungus Penicillium sp. CYE-87 Isolated from a Marine Tunicate

Lamiaa A. Shaala ^1,2 and Diaa T. A. Youssef ^3,*

¹ Natural Products Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia ² Suez Canal University Hospital, Suez Canal University, Ismailia 51522, Egypt ³ Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia

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