Ethyl 7-Acetyl-8a-methyl-3-(1-phenyl-1H-tetrazol-5-yl)-1,4,4a,5,6,8a-hexahydro-7H-pyrano[2,3-c]pyridazine-1-carboxylate

Susana M M Lopes,Teresa M V D Pinho E Melo,José A Paixão,Américo Lemos

doi:10.3390/m1338

Susana M M Lopes, Teresa M V D Pinho E Melo + Show 2 more

Open Access

https://doi.org/10.3390/m1338

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Journal: Molbank	Publication Date: Feb 10, 2022
Citations: 1	License type: CC BY 4.0

Affiliation: University of Coimbra, University of Algarve

Abstract

The Diels–Alder reaction of ethyl 3-(1-phenyl-1H-tetrazol-5-yl-1,2-diaza-1,3-butadiene-1-carboxylate with 2-acetyl-6-methyl-2,3-dihydro-4H-pyran (methyl vinyl ketone dimer) regioselectively afforded the corresponding 3-(tetrazol-5-yl)-hexahydro-7H-pyrano[2,3-c]pyridazine in quantitative yield. An X-ray crystal structure of this cycloadduct is reported.

Highlights

Conjugated nitrosoalkenes and azoalkenes are effective and versatile building blocks for the construction and functionalization of heterocyclic systems, acting mainly as electrondeficient heterodienes in hetero-Diels−Alder reactions or as Michael-type acceptors in conjugate 1,4-addition reactions [1]
Novel tryptophan analogues, where the carboxylic group was replaced by the bioisosteric tetrazolyl functionality, were obtained by exploring the reactivity of 3-tetrazolyl-nitrosoalkenes towards indoles, leading to indoles bearing open-chain oximes, followed by the oxime reduction
Molbank 2022, 2022, M1338 boxylic group was replaced by the bioisosteric tetrazolyl functionality, were obtained by boxylic group was replaced by the bioisosteric tetrazolyl functionality, were obtained by exploring the reactivity of 3-tetrazolyl-nitrosoalkenes towards indoles, leading to indoles exploring the reactivity of 3-tetrazolyl-nitrosoalkenes towards indoles, leading to indoles bearing open-chain oximes, followed by the oxime reduction. These tryptophan anabearing open-chain oximes, followed by the oxime reduction. These tryptophan analogues were used in the synthesis of biologically relevant β-carbolines containing a telogues were used in the synthesis of biologically relevant β-carbolines containing a tetrazole group via Pictet–Spengler condensation with aldehydes and further oxidation trazole group via Pictet–Spengler condensation with aldehydes and further oxidation β-carbolines containing a tetrazole group via Pictet–Spengler condensation with aldehydes and further oxidation

Summary

Introduction

Conjugated nitrosoalkenes and azoalkenes are effective and versatile building blocks for the construction and functionalization of heterocyclic systems, acting mainly as electrondeficient heterodienes in hetero-Diels−Alder reactions or as Michael-type acceptors in conjugate 1,4-addition reactions [1]. The tetrazole moiety displays stronger metabolic stability and several cases are known where the replacement of a carboxylate by a tetrazole group led to enhanced biological activity and metabolic stability [19,20,21] In this context, novel tryptophan analogues, where the carboxylic group was replaced by the bioisosteric tetrazolyl functionality, were obtained by exploring the reactivity of 3-tetrazolyl-nitrosoalkenes towards indoles, leading to indoles bearing open-chain oximes, followed by the oxime reduction. Novel tryptophan analogues, where the carboxylic group was replaced by the bioisosteric tetrazolyl functionality, were obtained by exploring the reactivity of 3-tetrazolyl-nitrosoalkenes towards indoles, leading to indoles bearing open-chain oximes, followed by the oxime reduction These tryptophan analogues were used in the synthesis of biologically relevant.

Synthesis

Results and

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General Information

Conclusions