Concise Synthesis of Naphthalene-Based 14-Aza-12-Oxasteroids
A concise, transition metal-free four-step synthetic pathway has been developed for the synthesis of tetracyclic heterosteroidal compounds, 14-aza-12-oxasteroids, starting from readily available 2-naphthol analogues. After conversion of 2-naphthols to 2-naphthylamines by the Bucherer reaction, subse...
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MDPI AG
2025-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/30/2/415 |
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| author | Smriti Srivastava Jun Luo Daniel Whalen Katherine N. Robertson Amitabh Jha |
| author_facet | Smriti Srivastava Jun Luo Daniel Whalen Katherine N. Robertson Amitabh Jha |
| author_sort | Smriti Srivastava |
| collection | DOAJ |
| description | A concise, transition metal-free four-step synthetic pathway has been developed for the synthesis of tetracyclic heterosteroidal compounds, 14-aza-12-oxasteroids, starting from readily available 2-naphthol analogues. After conversion of 2-naphthols to 2-naphthylamines by the Bucherer reaction, subsequent selective C-acetylation was achieved via the Sugasawa reaction and reduction of the acetyl group using borohydride, which resulted into the corresponding amino-alcohols. The naphthalene-based amino-alcohols underwent double dehydrations and double intramolecular cyclization with oxo-acids leading to one-pot formation of a C-N bond, a C-O bond and an amide bond in tandem, to generate two additional rings completing the steroidal framework. A series of 14-aza-12-oxasteroids were synthesized using our developed synthetic strategy in moderate yields, and the structure of one of the final products, 12a-Methyl-11-phenyl-11,12a-dihydro-1<i>H</i>-naphtho[2,1-d]pyrrolo[2,1-b][1,3]oxazin-3(2<i>H</i>)-one, was further confirmed by single crystal X-ray crystallography. |
| format | Article |
| id | doaj-art-2ff737cc04b14700a01d13d9e40cf437 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-2ff737cc04b14700a01d13d9e40cf4372025-01-24T13:43:57ZengMDPI AGMolecules1420-30492025-01-0130241510.3390/molecules30020415Concise Synthesis of Naphthalene-Based 14-Aza-12-OxasteroidsSmriti Srivastava0Jun Luo1Daniel Whalen2Katherine N. Robertson3Amitabh Jha4Department of Chemistry, Acadia University, Wolfville, NS B4P 2R6, CanadaDepartment of Chemistry, Acadia University, Wolfville, NS B4P 2R6, CanadaDepartment of Chemistry, Acadia University, Wolfville, NS B4P 2R6, CanadaDepartment of Chemistry, Saint Mary’s University, Halifax, NS B3H C3C, CanadaDepartment of Chemistry, Acadia University, Wolfville, NS B4P 2R6, CanadaA concise, transition metal-free four-step synthetic pathway has been developed for the synthesis of tetracyclic heterosteroidal compounds, 14-aza-12-oxasteroids, starting from readily available 2-naphthol analogues. After conversion of 2-naphthols to 2-naphthylamines by the Bucherer reaction, subsequent selective C-acetylation was achieved via the Sugasawa reaction and reduction of the acetyl group using borohydride, which resulted into the corresponding amino-alcohols. The naphthalene-based amino-alcohols underwent double dehydrations and double intramolecular cyclization with oxo-acids leading to one-pot formation of a C-N bond, a C-O bond and an amide bond in tandem, to generate two additional rings completing the steroidal framework. A series of 14-aza-12-oxasteroids were synthesized using our developed synthetic strategy in moderate yields, and the structure of one of the final products, 12a-Methyl-11-phenyl-11,12a-dihydro-1<i>H</i>-naphtho[2,1-d]pyrrolo[2,1-b][1,3]oxazin-3(2<i>H</i>)-one, was further confirmed by single crystal X-ray crystallography.https://www.mdpi.com/1420-3049/30/2/415heterosteroids14-aza-12-oxosteroidSugasawa reactionDean–Stark condensationdouble dehydration |
| spellingShingle | Smriti Srivastava Jun Luo Daniel Whalen Katherine N. Robertson Amitabh Jha Concise Synthesis of Naphthalene-Based 14-Aza-12-Oxasteroids Molecules heterosteroids 14-aza-12-oxosteroid Sugasawa reaction Dean–Stark condensation double dehydration |
| title | Concise Synthesis of Naphthalene-Based 14-Aza-12-Oxasteroids |
| title_full | Concise Synthesis of Naphthalene-Based 14-Aza-12-Oxasteroids |
| title_fullStr | Concise Synthesis of Naphthalene-Based 14-Aza-12-Oxasteroids |
| title_full_unstemmed | Concise Synthesis of Naphthalene-Based 14-Aza-12-Oxasteroids |
| title_short | Concise Synthesis of Naphthalene-Based 14-Aza-12-Oxasteroids |
| title_sort | concise synthesis of naphthalene based 14 aza 12 oxasteroids |
| topic | heterosteroids 14-aza-12-oxosteroid Sugasawa reaction Dean–Stark condensation double dehydration |
| url | https://www.mdpi.com/1420-3049/30/2/415 |
| work_keys_str_mv | AT smritisrivastava concisesynthesisofnaphthalenebased14aza12oxasteroids AT junluo concisesynthesisofnaphthalenebased14aza12oxasteroids AT danielwhalen concisesynthesisofnaphthalenebased14aza12oxasteroids AT katherinenrobertson concisesynthesisofnaphthalenebased14aza12oxasteroids AT amitabhjha concisesynthesisofnaphthalenebased14aza12oxasteroids |