Deprotection of Allyl Groups with Sulfinic Acids and Palladium Catalyst

Honda, Masaki; Morita, Hiromasa; Nagakura, Isao

doi:10.1021/jo971194c

Cited by 128 publications

(60 citation statements)

References 45 publications

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“…The phosphoramidite coupling method avoids transformation of lactol 20 to H -phosphonate 21 and the potential to competitively acylate 31 . To deprotect the acylsulfonamide 32 , a few allyl scavengers were tested (morpholine (30), p -toluenesulfinate (31), and barbituric acid (32)). Barbituric acid successfully removed allyl group from 32 under palladium catalysis to give free acylsulfonamide 33 .…”

Section: Resultsmentioning

confidence: 99%

Functional and Structural Analysis of a Key Region of the Cell Wall Inhibitor Moenomycin

Fuse

Tsukamoto

Yuan³

et al. 2010

ACS Chem. Biol.

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Moenomycin A (MmA) belongs to a family of natural products that inhibit peptidoglycan biosynthesis by binding to the peptidoglycan glycosyltransferases (PGTs), the enzymes that make the glycan chains of peptidoglycan. MmA is remarkably potent, but its clinical utility has been hampered by poor physicochemical properties. Moenomycin contains three structurally distinct regions: a pentasaccharide, a phosphoglycerate, and a C25 isoprenyl (moenocinyl) lipid tail that gives the molecule its name. The phosphoglycerate moiety links the pentasaccharide to the moenocinyl chain. This moiety contains two negatively charged groups, a phosphoryl group and a carboxylate. Both the phosphoryl group and the carboxylate have previously been implicated in target binding but the role of the carboxylate has not been explored in detail. Here we report the synthesis of six MmA analogs designed to probe the importance of the phosphoglycerate. These analogs were evaluated for antibacterial and enzyme inhibitory activity; the specific contacts between the phosphoglycerate and the protein target were assessed by X-ray crystallography in conjunction with molecular modeling. Both the phosphoryl group and the carboxylate of the phosphoglycerate chain play roles in target binding. The negative charge of the carboxylate, and not its specific structure, appears to be the critical feature in binding since replacing it with a negatively charged acylsulfonamide group produces a more active compound than replacing it with the isosteric amide. Analysis of the ligand-protein contacts suggests that the carboxylate makes a critical contact with an invariant lysine in the active site. The reported work provides information and validated computational methods critical for the design of analogs based on moenomycin scaffolds.

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Section: Resultsmentioning

confidence: 99%

Functional and Structural Analysis of a Key Region of the Cell Wall Inhibitor Moenomycin

Fuse

Tsukamoto

Yuan³

et al. 2010

ACS Chem. Biol.

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“…Conventional methods for cleavage of the allyl group combine a transition metal-catalyzed isomerization of the double bond to the enol ether and subsequent hydrolysis of the latter to produce the corresponding alcohol (26,27). For application in SBS, it is important to ensure that complete chemical cleavage of the 3Ј-O-allyl group can be rapidly and specifically carried out while leaving the DNA intact.…”

Section: Resultsmentioning

confidence: 99%

Design and synthesis of a 3′- O -allyl photocleavable fluorescent nucleotide as a reversible terminator for DNA sequencing by synthesis

Ruparel

Bi²,

Li³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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DNA sequencing by synthesis (SBS) offers an approach for potential high-throughput sequencing applications. In this method, the ability of an incoming nucleotide to act as a reversible terminator for a DNA polymerase reaction is an important requirement to unambiguously determine the identity of the incorporated nucleotide before the next nucleotide is added. A free 3 -OH group on the terminal nucleotide of the primer is necessary for the DNA polymerase to incorporate an incoming nucleotide. Therefore, if the 3 -OH group of an incoming nucleotide is capped by a chemical moiety, it will cause the polymerase reaction to terminate after the nucleotide is incorporated into the DNA strand. If the capping group is subsequently removed to generate a free 3 -OH, the polymerase reaction will reinitialize. We report here the design and synthesis of a 3 -modified photocleavable fluorescent nucleotide, 3 -O-allyl-dUTP-PC-Bodipy-FL-510 (PC-Bodipy, photocleavable 4,4-difluoro-4-bora-3␣,4␣-diaza-s-indacene), as a reversible terminator for SBS. This nucleotide analogue contains an allyl moiety capping the 3 -OH group and a fluorophore Bodipy-FL-510 linked to the 5 position of the uracil through a photocleavable 2-nitrobenzyl linker. Here, we have shown that this nucleotide is a good substrate for a DNA polymerase. After the nucleotide was successfully incorporated into a growing DNA strand and the fluorophore was photocleaved, the allyl group was removed by using a Pd-catalyzed reaction to reinitiate the polymerase reaction, thereby establishing the feasibility of using such nucleotide analogues as reversible terminators for SBS. 2-nitrobenzyl linker ͉ photocleavageT he completion of the Human Genome Project (1, 2) has led to an increased demand for high-throughput and rapid DNA sequencing methods to identify genetic variants for applications in pharmacogenomics (3), disease gene discovery (4, 5), and gene function studies (6). Current state-of-the-art DNA sequencing technologies (7-11) to some extent address the accuracy and throughput requirements but suffer limitations with respect to cost and data quality. Thus, a new DNA sequencing approach is required to broaden the applications of genomic information in medical research and health care. In this regard, DNA sequencing by synthesis (SBS) offers an alternative approach to possibly address the limitations of current DNA sequencing techniques. We have previously described the design of a parallel chip-based SBS system, which uses a self-priming DNA template covalently linked to the glass surface of a chip and four modified nucleotides (12-14). The nucleotides are modified such that they have a photocleavable fluorescent moiety attached to the base (5 position of pyrimidines, 7 position of purines) and a chemically cleavable group to cap the 3Ј-OH. When the correct nucleotide is incorporated in a DNA polymerase reaction, specific to the template sequence, the reaction is temporarily terminated because of the lack of a free 3Ј-OH group. After the fluorescent signal is detected ...

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“…In this case, amino acid from Set 2 [Fmoc-LHis(Trt)-OH, Fmoc-L-Ala-OH, Fmoc-L-Leu-OH, Fmoc-LPro-OH, Fmoc-L-Tyr( t Bu)-OH, Fmoc-L-Asn(Trt)-OH] and their Boc-protected counterparts were used to afford 4. After pooling, the Aloc group was removed by Pd-catalyzed allyl transfer to anilinium p-toluenesulfinate 10,17 Finally, Fmoc-cleavage followed by global deprotection of all functionalized side chains as well as Boc cleavage using TFA/TIS/H 2 O was performed and the fully deprotected TAC-based library 6 was obtained. The large and highly diverse library, containing 46,656 different receptors (6 6 ), was now ready for screening of selective binding by specific peptide sequences.…”

Section: Resultsmentioning

confidence: 99%

Combinatorial solid-phase synthesis and screening of a diverse tripodal triazacyclophane (TAC)-based synthetic receptor library showing a remarkable selectivity towards a d-Ala-d-Ala containing ligand

2004

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Deprotection of Allyl Groups with Sulfinic Acids and Palladium Catalyst

Cited by 128 publications

References 45 publications

Functional and Structural Analysis of a Key Region of the Cell Wall Inhibitor Moenomycin

Functional and Structural Analysis of a Key Region of the Cell Wall Inhibitor Moenomycin

Design and synthesis of a 3′- O -allyl photocleavable fluorescent nucleotide as a reversible terminator for DNA sequencing by synthesis

Combinatorial solid-phase synthesis and screening of a diverse tripodal triazacyclophane (TAC)-based synthetic receptor library showing a remarkable selectivity towards a d-Ala-d-Ala containing ligand

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