Synthesis and properties of the eight isostatine stereoisomers

Rinehart, Kenneth L.; Sakai, Ryuichi; Kishore, Vimal; Sullins, David W.; Li, Kai Ming

doi:10.1021/jo00037a012

Cited by 36 publications

(44 citation statements)

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“…[15,16] The key feature of this Scheme was expected to be a highly convergent assembly of 5 and 6 by direct condensation of segment 7 or 8 with segment 9. Segments 7 and 8 would be prepared via an aldol coupling of N-Boc-d-valinal (10) [19] or d-allo-isoleucinal (11) [20] with ethyl acetate (12), and subsequent condensation with d-cysteine dervative 13.…”

Section: Resultsmentioning

confidence: 99%

“…As shown in Scheme 7, the synthesis of segment 8 was conducted starting from N-Boc-d-allo-isoleucinal (11) [20] by employing a reaction sequence similar to that described in the section on the synthesis of segment 7 (cf. Scheme 2).…”

Section: Synthesis Of Segmentmentioning

confidence: 99%

“…Completion of the total synthesis of 5''-epi-spiruchostatin B (52): As shown in Scheme 9, using (2R,3R)-N-Boc-d-isoleucinal (50) [20] instead of (2R,3S)-N-Boc-d-allo-isoleucinal (11) as the starting material, 5''-epi-spiruchostatin B (52) was synthesized through condensation of segments 51 and 9 in the same manner as described for the synthesis of spiruchostatin B (2) (cf. Schemes 7 and 8).…”

Section: Synthesis Of Segmentmentioning

confidence: 99%

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Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A and B, 5′′‐epi‐Spiruchostatin B, FK228 (FR901228) and Preliminary Evaluation of Their Biological Activity

Narita

Kikuchi

Watanabe

et al. 2009

Chemistry A European J

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The bicyclic depsipeptide histone deacetylase (HDAC) inhibitors spiruchostatins A and B, 5''-epi-spiruchostatin B and FK228 were efficiently synthesized in a convergent and unified manner. The synthetic method involved the following crucial steps: i) a Julia-Kocienski olefination of a 1,3-propanediol-derived sulfone and a L- or D-malic acid-derived aldehyde to access the most synthetically challenging unit, (3S or 3R,4E)-3-hydroxy-7-mercaptohept-4-enoic acid, present in a D-alanine- or D-valine-containing segment; ii) a condensation of a D-valine-D-cysteine- or D-allo-isoleucine-D-cysteine-containing segment with a D-alanine- or D-valine-containing segment to directly assemble the corresponding seco-acids; and iii) a macrocyclization of a seco-acid using the Shiina method or the Mitsunobu method to construct the requisite 15- or 16-membered macrolactone. The present synthesis has established the C5'' stereochemistry of spiruchostatin B. In addition, HDAC inhibitory assay and the cell-growth inhibition analysis of the synthesized depsipeptides determined the order of their potency and revealed some novel aspects of structure-activity relationships. It was also found that unnatural 5''-epi-spiruchostatin B shows extremely high selectivity (ca. 1600-fold) for class I HDAC1 (IC(50)=2.4 nM) over class II HDAC6 (IC(50)=3900 nM) with potent cell-growth-inhibitory activity at nanomolar levels of IC(50) values.

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Section: Resultsmentioning

confidence: 99%

Section: Synthesis Of Segmentmentioning

confidence: 99%

Section: Synthesis Of Segmentmentioning

confidence: 99%

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Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A and B, 5′′‐epi‐Spiruchostatin B, FK228 (FR901228) and Preliminary Evaluation of Their Biological Activity

Narita

Kikuchi

Watanabe

et al. 2009

Chemistry A European J

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“…However, reports in the literature indicated that 4-amino-3-hydroxy-5-methylheptanoic acid, found in the didemnins, underwent an epimerization at C-3 via an acid-catalyzed dehydration/hydration sequence, and that significant quantities of the intermediate a,/3-unsaturated acid existed after prolonged hydrolysis. 12 This suggested the absolute configuration of C-29 could be determined by acid hydrolysis and subsequent ozonolysis, with oxidative workup, to D-or L-valine. This was indeed the case and chiral HPLC showed unambiguously that C-29 was derived from L-valine.…”

Section: Resultsmentioning

confidence: 99%

Continuing Studies on the Cyanobacterium Lyngbya sp.: Isolation and Structure Determination of 15-Norlyngbyapeptin A and Lyngbyabellin D

et al. 2003

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Re-collections of the cyanobacterium Lyngbya sp. have yielded two more members of the lyngbyapeptin and lyngbyabellin families. The gross structures of 15-norlyngbyapeptin A (1) and lyngbyabellin D (3) were deduced through standard 2D NMR techniques, with the absolute configuration of both elucidated through degradation and comparison with commercially available and synthetic standards. Degradation to the a-amino acid and NOE correlations determined the absolute and relative configuration of the 4-amino-3-hydroxy-5-methylhexanoic acid unit in 3. Lyngbyabellin D (3) displayed an IC50 value of 0.1 jiiM. against the KB cell line.The innumerable environmental pressures faced by marine cyanobacteria have undoubtedly catalyzed a tremendous genetic diversity, which often manifests itself in the production of secondary metabolites. By one estimate, almost 10% of the cyanobacterial genome may be devoted to this cause. 1 We have spent the past few years involved in the chemical characterization of secondary metabolites from a particular strain of Lyngbya sp. (Oscillatoriaceae) found in Palau and Guam. 2 This field-collected cyanobacterium, easily identifiable by the presence of a small shrimp 3 within the algal mat, produces an extraordinary array of secondary metabolites. Collections of this cyanobacterium made over the previous 10 years have yielded eight distinct classes of metabolites, consisting of some 26 different compounds. 24 Results and DiscussionSeveral large re-collections of the cyanobacterium were undertaken in Guam during the Spring of 2002 to facilitate further biological evaluation of two of these cytotoxins, the apratoxins 4 and lyngbyabellins. 2a Reported here are the isolation and structure determination, from these extracts, of 15-norlyngbyapeptin A (1) and lyngbyabellin D (3), which were both isolated in 3 x 10~4% of the cyanobacterium's dry weight. Lyngbyabellin D (3) displayed an IC50 value of 0.1 fiM against the KB cell line. 5 The richly detailed proton NMR spectrum of 1 ( a The numbering system for lyngbyapeptin A (2) has been adopted. 6a The NMR spectra of 1 and lyngbyapeptin A (2) were nearly superimposable, but 1 lacked the signals for the aromatic methoxy group on the tyrosine unit (C-15), which established 1 as 15-norlyngbyapeptin A. Fragments derived from 10

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“…There is no general method for determining the configuration of the chiral centers in γ-amino-β-hydroxy acids. However, Rinehart reported that 4-amino-3-hydroxy-5-methylheptanoic acid underwent an epimerization at C-3 via an acid-catalyzed dehydration/hydration sequence, and that significant quantities of the intermediate α, β-unsaturated acid existed after prolonged hydrolysis (Rinehart et al, 1992). The efforts toward finding novel marine cyanobacterial metabolites with antitumor activity led to the isolation of bisebromoamide from a Lyngbya sp.…”

Section: Acyclic Polypeptidesmentioning

confidence: 99%

Absolute Configuration and Biosynthesis of Pahayokolide A from Lyngbya sp. Strain 15-2 of the Florida Everglades

Liu¹

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Synthesis and properties of the eight isostatine stereoisomers

Cited by 36 publications

References 0 publications

Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A and B, 5′′‐epi‐Spiruchostatin B, FK228 (FR901228) and Preliminary Evaluation of Their Biological Activity

Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A and B, 5′′‐epi‐Spiruchostatin B, FK228 (FR901228) and Preliminary Evaluation of Their Biological Activity

Continuing Studies on the Cyanobacterium Lyngbya sp.: Isolation and Structure Determination of 15-Norlyngbyapeptin A and Lyngbyabellin D

Absolute Configuration and Biosynthesis of Pahayokolide A from Lyngbya sp. Strain 15-2 of the Florida Everglades

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