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Total synthesis of the putative structure of the proposed Banyasin A.

Gao X, Ren Q, Choi S, Xu Z, Ye T - Front Chem (2015)

Bottom Line: The first total synthesis of four possible isomers of a molecule possessing the configuration proposed for Banyasin A is described.The structure synthesized appears to be different from that of the natural product.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Shenzhen, China.

ABSTRACT
The first total synthesis of four possible isomers of a molecule possessing the configuration proposed for Banyasin A is described. The structure synthesized appears to be different from that of the natural product.

No MeSH data available.


The Structures of banyasin A (1), argifin and argadin.
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Figure 1: The Structures of banyasin A (1), argifin and argadin.

Mentions: In 2005, Carmeli and Pluotno reported the isolation of banyasin A (1) (Figure 1), from cyanobacterium Nostoc sp. (Pluotno and Carmeli, 2005). Structurally, banyasin A possesses a 16-membered macrocyclic peptide backbone which is composed of the unique, non-proteinogenic amino acids residues such as 3-amino-2-methyl-5E-octenoic acid and L-N8-(N-methylcarboxyaminde)arginine. Both the relative stereochemistry and absolute configuration of 3-amino-2-methyl-5E-octeneoic acid were unassigned in the isolation paper. The final structural determination had to await the total synthesis of the four possible diastereomeric structures proposed for the natural product. Banyasin A was isolated followed by a serine protease inhibition-guided protocol, however, pure banyasin A was found to be inactive toward trypsin inhibition. Banyasin A is structurally closely related to the known chitinase inhibitors argifin and argadin (Figure 1) (Arai et al., 2000; Omura et al., 2000). All these three natural products contained a highly modified arginine at the guanidine moiety. It is known that the dimethylguanylurea fragment of argifin was found to harbor all significant interactions with the chitinase and binds with unusually high efficiency. (Andersen et al., 2008). L-N8-(N-methylcarboxyaminde)arginine moiety played the critical role in binding of argifin to its cognate target (Dixon et al., 2009). The 16-membered macrolactam ring of banyasin A resemble the macrocyclic core of the known chitinase inhibitor argifin. Both banyasin A and argifin are comprised of L-N8-(N-methylcarboxyaminde)arginine residue. Modeling studies based on conformational analysis and manual docking yielded a binding model of banyasin A to a fungal chitinase (AfChiB1) active site, which has the most similar binding mode of argifin to AfChiB1 (Rao et al., 2005). As a representative compound, 1b was displayed in Figure 2. The rest binding modes of banyasin's diastereomers (1a, 1c, and 1d) in AfChiB1 active site were included in support information. Taken together, these studies implied that banyasin A may serve as a potential lead compound for the development of antifungals and pesticides. The limited supply of banyasin A from its natural source has prevented its full biological characterization. In order to obtain sufficient material for more extensive biological evaluation as well as to determine the absolute configuration of banyasin A, we undertook research to develop a total synthesis of banyasin A with flexibility to enable future SAR development. Herein, we describe our efforts toward the total synthesis of banyasin A.


Total synthesis of the putative structure of the proposed Banyasin A.

Gao X, Ren Q, Choi S, Xu Z, Ye T - Front Chem (2015)

The Structures of banyasin A (1), argifin and argadin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362330&req=5

Figure 1: The Structures of banyasin A (1), argifin and argadin.
Mentions: In 2005, Carmeli and Pluotno reported the isolation of banyasin A (1) (Figure 1), from cyanobacterium Nostoc sp. (Pluotno and Carmeli, 2005). Structurally, banyasin A possesses a 16-membered macrocyclic peptide backbone which is composed of the unique, non-proteinogenic amino acids residues such as 3-amino-2-methyl-5E-octenoic acid and L-N8-(N-methylcarboxyaminde)arginine. Both the relative stereochemistry and absolute configuration of 3-amino-2-methyl-5E-octeneoic acid were unassigned in the isolation paper. The final structural determination had to await the total synthesis of the four possible diastereomeric structures proposed for the natural product. Banyasin A was isolated followed by a serine protease inhibition-guided protocol, however, pure banyasin A was found to be inactive toward trypsin inhibition. Banyasin A is structurally closely related to the known chitinase inhibitors argifin and argadin (Figure 1) (Arai et al., 2000; Omura et al., 2000). All these three natural products contained a highly modified arginine at the guanidine moiety. It is known that the dimethylguanylurea fragment of argifin was found to harbor all significant interactions with the chitinase and binds with unusually high efficiency. (Andersen et al., 2008). L-N8-(N-methylcarboxyaminde)arginine moiety played the critical role in binding of argifin to its cognate target (Dixon et al., 2009). The 16-membered macrolactam ring of banyasin A resemble the macrocyclic core of the known chitinase inhibitor argifin. Both banyasin A and argifin are comprised of L-N8-(N-methylcarboxyaminde)arginine residue. Modeling studies based on conformational analysis and manual docking yielded a binding model of banyasin A to a fungal chitinase (AfChiB1) active site, which has the most similar binding mode of argifin to AfChiB1 (Rao et al., 2005). As a representative compound, 1b was displayed in Figure 2. The rest binding modes of banyasin's diastereomers (1a, 1c, and 1d) in AfChiB1 active site were included in support information. Taken together, these studies implied that banyasin A may serve as a potential lead compound for the development of antifungals and pesticides. The limited supply of banyasin A from its natural source has prevented its full biological characterization. In order to obtain sufficient material for more extensive biological evaluation as well as to determine the absolute configuration of banyasin A, we undertook research to develop a total synthesis of banyasin A with flexibility to enable future SAR development. Herein, we describe our efforts toward the total synthesis of banyasin A.

Bottom Line: The first total synthesis of four possible isomers of a molecule possessing the configuration proposed for Banyasin A is described.The structure synthesized appears to be different from that of the natural product.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Shenzhen, China.

ABSTRACT
The first total synthesis of four possible isomers of a molecule possessing the configuration proposed for Banyasin A is described. The structure synthesized appears to be different from that of the natural product.

No MeSH data available.