Efficacious N-protection of O-aryl sulfamates with 2,4-dimethoxybenzyl groups.

doi:10.1039/c2ob26057c

Paper

Efficacious N-protection of O-aryl sulfamates with 2,4-dimethoxybenzyl groups.

Published Aug 30, 2012 · Tristan Reuillon, A. Bertoli, R. Griffin

Organic & biomolecular chemistry

Q2 SJR score

8

Citations

0

Influential Citations

Full textSemantic Scholar

Abstract

Sulfamates are important functional groups in certain areas of current medicinal chemistry and drug development. Alcohols and phenols are generally converted into the corresponding primary sulfamates (ROSO(2)NH(2) and ArOSO(2)NH(2), respectively) by reaction with sulfamoyl chloride (H(2)NSO(2)Cl). The lability of the O-sulfamate group, especially to basic conditions, usually restricts this method to a later stage of a synthesis. To enable a more flexible approach to the synthesis of phenolic O-sulfamates, a protecting group strategy for sulfamates has been developed. Both sulfamate NH protons were replaced with either 4-methoxybenzyl or 2,4-dimethoxybenzyl. These N-protected sulfamates were stable to oxidising and reducing agents, as well as bases and nucleophiles, thus rendering such masked sulfamates suitable for multi-step synthesis. The protected sulfamates were synthesised by microwave heating of 1,1'-sulfonylbis(2-methyl-1H-imidazole) with a substituted phenol to give an aryl 2-methyl-1H-imidazole-1-sulfonate. This imidazole-sulfonate was N-methylated by reaction with trimethyloxonium tetrafluoroborate, which enabled subsequent displacement of 1,2-dimethylimidazole by a dibenzylamine (e.g. bis-2,4-dimethoxybenzylamine). The resulting N-diprotected, ring-substituted phenol O-sulfamates were further manipulated through reactions at the aryl substituent and finally deprotected with trifluoroacetic acid to afford a phenol O-sulfamate. The use of 2,4-dimethoxybenzyl was particularly attractive because deprotection occurred quantitatively within 2 h at room temperature with 10% trifluoroacetic acid in dichloromethane. The four key steps in the protocol described [reaction of 1,1'-sulfonylbis(2-methyl-1H-imidazole) with a phenol, methylation, displacement with a dibenzylamine and deprotection] all proceeded in very high yields.

Study Snapshot

This study developed a flexible, efficient method for synthesising phenolic O-sulfamates using 2,4-dimethoxybenzyl groups, enabling multi-step synthesis in medicinal chemistry and drug development.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Efficacious N-protection of O-aryl sulfamates with 2,4-dimethoxybenzyl groups.

Sign up to use Study Snapshot

References

Preparation of trifluoroethyl- and phenyl-protected sulfates using sulfuryl imidazolium salts

Sulfuryl imidazolium salts with TFE and phenyl groups are effective sulfating agents for preparing TFE-protected phenolic and carbohydrate sulfates, improving upon previous methods.

Design and synthesis of an androgen receptor pure antagonist (CH5137291) for the treatment of castration-resistant prostate cancer.

CH5137291 is a potent androgen receptor pure antagonist that effectively inhibits tumor growth in a castration-resistant prostate cancer model without producing agonist metabolites.

Copper-free palladium-catalyzed Sonogashira and Hiyama cross-couplings using aryl imidazol-1-ylsulfonates

Copper-free palladium-catalyzed Sonogashira and Hiyama cross-couplings using aryl imidazol-1-ylsulfonates effectively produce phenylacetylene derivatives in excellent yield.

S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases.

S-glycosyl primary sulfonamides show moderate potency in selectively inhibiting cancer-associated carbonic anhydrases, offering potential for future cancer treatments.

O- and N-sulfations of carbohydrates using sulfuryl imidazolium salts.

SIS 9 is a superior sulfating agent for carbohydrates, enabling high yields and easier access to difficult-to-sulfate compounds.

2009 Edward E Smissman Award. Pharmaceutical "gold" from neurostabilizing agents: topiramate and successor molecules.

Topiramate and its successor molecules have revolutionized epilepsy treatment and migraine prevention, proving that neurostabilizing agents can be effective drugs for treating various diseases.

Imidazolylsulfonates: electrophilic partners in cross-coupling reactions.

Imidazolylsulfonates are a practical and economical alternative to triflates in palladium-mediated cross-coupling reactions, offering good stability and reactivity while maintaining good reactivity.

Synthesis of S-glycosyl primary sulfonamides.

This study presents a novel method for synthesizing S-glycosyl primary sulfonamides at the anomeric position of carbohydrates, offering potential applications in pharmaceutical and biotechnology industries.

Efficient solid-phase synthesis of sulfotyrosine peptides using a sulfate protecting-group strategy.

Efficient solid-phase synthesis of sulfotyrosine peptides can be achieved using a sulfate protecting-group strategy, resulting in high yields and easy removal of protecting groups.

Citations

Acid-Mediated Imidazole-to-Fluorine Exchange for the Synthesis of Sulfonyl and Sulfonimidoyl Fluorides.

This study presents a single-step procedure for preparing sulfur(VI) fluorides from sulfonyl imidazoles, providing good to excellent yields of various sulfonyl, sulfonimidoyl, sulfoxyl, and sul

Photochemically-Mediated, Nickel-Catalyzed Synthesis of N-(Hetero)aryl Sulfamate Esters.

This method enables the synthesis of N-(hetero)aryl sulfamate esters under mild conditions, avoiding undesirable N-alkylation in palladium-based protocols.

Introduction of Para-Hydroxy Benzyl Spacer Greatly Expands the Utility of Ortho-Hydroxy-Protected Aryl Sulfate System: Application to Nonphenolic Payloads.

The para-hydroxy benzyl spacer enhances the stability and smooth release of nonphenolic payloads in the ortho-hydroxy-protected aryl sulfate system, making it a promising tool for targeted delivery of nonphenolic payloads.

Esters of levonorgestrel and etonogestrel intended as single, subcutaneous-injection, long-lasting contraceptives

A single-dose injectable contraceptive using levonorgestrel and etonogestrel esters showed superior anti-ovulatory activity in murine models, with a LNG-phenoxyacetic acid ester analog inhibiting ovulation for 60 days compared to medroxypro

O-(Aminosulfonylation) of phenols and an example of slow hydrolytic release

This study demonstrates a method to create a library of 114 sulfamate esters, Ar-OSO2-NR2, with a sulfamate-based conjugate of ethinyl estradiol, resulting in slow hydrolytic release with half-lives of 6.

Efficacious N‐Protection of O‐Aryl Sulfamates with 2,4‐Dimethoxybenzyl Groups.

This method effectively protects O-aryl sulfamates with 2,4-dimethoxybenzyl groups, enabling the synthesis of various pharmaceuticals and nutraceuticals.