A Local Desymmetrization Approach to Piperidinyl Acetic Acid γ‑Secretase Modulators
A desymmetrization-based approach for the synthesis of piperidinyl acetic acid γ-secretase modulators has been developed. The synthetic sequence features the use of N-tert-butanesulfinyl imine reduction and a diastereoselective lactam formation to set up the chiral centers. The synthetic utility is...
Saved in:
| Published in | Journal of organic chemistry Vol. 86; no. 21; pp. 15481 - 15487 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
WASHINGTON
American Chemical Society
05.11.2021
Amer Chemical Soc |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | A desymmetrization-based approach for the synthesis of piperidinyl acetic acid γ-secretase modulators has been developed. The synthetic sequence features the use of N-tert-butanesulfinyl imine reduction and a diastereoselective lactam formation to set up the chiral centers. The synthetic utility is demonstrated by the concise asymmetric synthesis of γ-secretase modulator GSM-1. |
|---|---|
| AbstractList | A desymmetrization-based approach for the synthesis of piperidinyl acetic acid gamma-secretase modulators has been developed. The synthetic sequence features the use of N-tert-butanesulfinyl imine reduction and a diastereoselective lactam formation to set up the chiral centers. The synthetic utility is demonstrated by the concise asymmetric synthesis of gamma-secretase modulator GSM-1. A desymmetrization-based approach for the synthesis of piperidinyl acetic acid γ-secretase modulators has been developed. The synthetic sequence features the use of -butanesulfinyl imine reduction and a diastereoselective lactam formation to set up the chiral centers. The synthetic utility is demonstrated by the concise asymmetric synthesis of γ-secretase modulator GSM-1. A desymmetrization-based approach for the synthesis of piperidinyl acetic acid γ-secretase modulators has been developed. The synthetic sequence features the use of N-tert-butanesulfinyl imine reduction and a diastereoselective lactam formation to set up the chiral centers. The synthetic utility is demonstrated by the concise asymmetric synthesis of γ-secretase modulator GSM-1. |
| Author | Zu, Liansuo Lu, Haigen Cheng, Peng |
| AuthorAffiliation | School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure |
| AuthorAffiliation_xml | – name: School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure |
| Author_xml | – sequence: 1 givenname: Peng surname: Cheng fullname: Cheng, Peng – sequence: 2 givenname: Haigen surname: Lu fullname: Lu, Haigen – sequence: 3 givenname: Liansuo orcidid: 0000-0001-7747-2979 surname: Zu fullname: Zu, Liansuo email: zuliansuo@tsinghua.edu.cn |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34641679$$D View this record in MEDLINE/PubMed |
| BookMark | eNqNkctKxDAUhoMoOqOu3UmXgnTMpU2b5TBeYUTBy7Zk0lOMtM2YpMi48hV8Ft_Dh_BJzDjjuBLMIieEL-f8fOmj9da0gNAewQOCKTmSyg0ejRoQhYnI8BrqkZTimAucrKMexpTGjHK2hfrOPeKw0jTdRFss4Qnhmeih-2E0NkrW0TG4WdOAt_pFem3aaDidWiPVQ-RNdK2nYHWp21kdDRV4rULRZfTx_vn6dgPKgpcOoktTdrX0xrodtFHJ2sHusm6ju9OT29F5PL46uxgNx7FkjPmYhmwJZZiDErxMJEzSkgsa9rSSeR6ucpbiDCBJMkxkJQRPoKoo50pQxSdsGx0s-oasTx04XzTaKahr2YLpXEHTnOSUZnkW0KMFqqxxzkJVTK1upJ0VBBdzmUWQWQSZxVJmeLG_bN5NGihX_I-9ABwugGeYmMopDa2CFRZsZwHLchZOYk7n_6dH2n9_w8h0rf8dtIjY2TZI_TP3FwhXo2w |
| CitedBy_id | crossref_primary_10_3390_ijms24032937 crossref_primary_10_1016_j_tetlet_2022_153776 |
| Cites_doi | 10.1002/ejoc.201601481 10.1002/asia.201402865 10.1021/jo4020547 10.1002/chem.201602900 10.1039/d0md00196a 10.1016/j.ejmech.2018.02.035 10.1021/jo0609834 10.1021/jacs.7b12898 10.1016/j.bmcl.2009.08.072 10.1002/anie.201810974 10.1021/acs.orglett.7b02735 10.1039/D0MD00196A 10.1021/ar020066u |
| ContentType | Journal Article |
| Copyright | 2021 American Chemical Society |
| Copyright_xml | – notice: 2021 American Chemical Society |
| DBID | 1KM 1KN BLEPL DTL HGBXW CGR CUY CVF ECM EIF NPM AAYXX CITATION 7X8 |
| DOI | 10.1021/acs.joc.1c01970 |
| DatabaseName | Index Chemicus Current Chemical Reactions Web of Science Core Collection Science Citation Index Expanded Web of Science - Science Citation Index Expanded - 2021 Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef MEDLINE - Academic |
| DatabaseTitle | Web of Science MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef MEDLINE - Academic |
| DatabaseTitleList | Web of Science MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 1KN name: Current Chemical Reactions url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/woscc/search-with-editions?editions=WOS.CCR sourceTypes: Enrichment Source Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Chemistry |
| EISSN | 1520-6904 |
| EndPage | 15487 |
| ExternalDocumentID | 10_1021_acs_joc_1c01970 34641679 000716778300099 d8509458 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GrantInformation_xml | – fundername: National Key R&D Program of China grantid: 2020YFA0509300 |
| GroupedDBID | - 29L 4.4 53G 55A 5RE 5VS 7~N 85S AABXI ABFLS ABFRP ABMVS ABPPZ ABPTK ABUCX ACGFS ACJ ACNCT ACS AEESW AENEX AFEFF ALMA_UNASSIGNED_HOLDINGS AQSVZ BAANH CS3 D0L DU5 DZ EBS ED F5P GGK GNL IH2 IH9 IHE JG K2 LG6 P2P PZZ ROL RXW TAE TN5 UI2 UKR UPT VF5 VG9 VQA W1F WH7 X XFK YZZ --- -DZ -~X .K2 1KM 1KN AAHBH ABJNI ABQRX ACBEA ACGFO ADHLV AGXLV AHGAQ BLEPL CUPRZ DTL ED~ GROUPED_WOS_SCIENCE_CITATION_INDEX_EXPANDED JG~ TAF XSW YQT ZCA CGR CUY CVF ECM EIF NPM AAYXX CITATION 7X8 |
| ID | FETCH-LOGICAL-a333t-226342306ec96d4aeb5d692b5d5fa886d483507ee44701af9964eff266c92c6b3 |
| IEDL.DBID | ACS |
| ISICitedReferencesCount | 3 |
| ISICitedReferencesURI | https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestApp=WOS&DestLinkType=CitingArticles&UT=000716778300099 |
| ISSN | 0022-3263 |
| IngestDate | Sat Aug 17 02:47:43 EDT 2024 Fri Aug 23 04:03:35 EDT 2024 Sat Sep 28 08:22:37 EDT 2024 Wed Sep 18 10:25:51 EDT 2024 Fri Nov 08 20:09:22 EST 2024 Sat Nov 13 04:46:05 EST 2021 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 21 |
| Keywords | ASYMMETRIC-SYNTHESIS |
| Language | English |
| LinkModel | DirectLink |
| LogoURL | https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg |
| MergedId | FETCHMERGED-LOGICAL-a333t-226342306ec96d4aeb5d692b5d5fa886d483507ee44701af9964eff266c92c6b3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0001-7747-2979 |
| PMID | 34641679 |
| PQID | 2581822787 |
| PQPubID | 23479 |
| PageCount | 7 |
| ParticipantIDs | proquest_miscellaneous_2581822787 crossref_primary_10_1021_acs_joc_1c01970 webofscience_primary_000716778300099 pubmed_primary_34641679 acs_journals_10_1021_acs_joc_1c01970 webofscience_primary_000716778300099CitationCount |
| PublicationCentury | 2000 |
| PublicationDate | 20211105 2021-11-05 |
| PublicationDateYYYYMMDD | 2021-11-05 |
| PublicationDate_xml | – month: 11 year: 2021 text: 20211105 day: 05 |
| PublicationDecade | 2020 |
| PublicationPlace | WASHINGTON |
| PublicationPlace_xml | – name: WASHINGTON – name: United States |
| PublicationTitle | Journal of organic chemistry |
| PublicationTitleAbbrev | J ORG CHEM |
| PublicationTitleAlternate | J. Org. Chem |
| PublicationYear | 2021 |
| Publisher | American Chemical Society Amer Chemical Soc |
| Publisher_xml | – name: American Chemical Society – name: Amer Chemical Soc |
| References | (000716778300099.4) 2013 Colyer, JT (WOS:000240020100020) 2006; 71 Horwitz, MA (WOS:000397849300001) 2017; 2017 Horwitz, MA (WOS:000414723900018) 2017; 19 Kumar, D (WOS:000428824700035) 2018; 148 Park, J (WOS:000452235600035) 2018; 57 Murai, K (WOS:000345513900019) 2014; 9 Hall, A (WOS:000273783800116) 2010; 20 Nugent, TC (WOS:000384698200031) 2016; 22 Liu, Y (WOS:000328231600040) 2013; 78 (000716778300099.3) 2006 Ellman, JA (WOS:000179410200008) 2002; 35 Mekala, S (WOS:000571976500009) 2020; 11 Tan, XF (WOS:000425475300011) 2018; 140 ref9/cit9 ref6/cit6 ref3/cit3 ref4/cit4a ref4/cit4b ref4/cit4c ref2/cit2c ref2/cit2b ref5/cit5 ref2/cit2a ref1/cit1a ref4/cit4d ref1/cit1b ref7/cit7 |
| References_xml | – volume: 2017 start-page: 1381 year: 2017 ident: WOS:000397849300001 article-title: Local Desymmetrization through Diastereotopic Group Selection: An Enabling Strategy for Natural Product Synthesis publication-title: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY doi: 10.1002/ejoc.201601481 contributor: fullname: Horwitz, MA – year: 2013 ident: 000716778300099.4 publication-title: Piperidines and related compounds for the treatment of Alzheimer ' s disease – volume: 9 start-page: 3511 year: 2014 ident: WOS:000345513900019 article-title: Enantioselective, Desymmetrizing, Bromolactonization Reactions of Symmetric Olefinic Dicarboxylic Acids publication-title: CHEMISTRY-AN ASIAN JOURNAL doi: 10.1002/asia.201402865 contributor: fullname: Murai, K – volume: 78 start-page: 12009 year: 2013 ident: WOS:000328231600040 article-title: Enantioselective Synthesis of Indoloquinolizidines via Asymmetric Catalytic Hydrogenation/Lactamization of Imino Diesters publication-title: JOURNAL OF ORGANIC CHEMISTRY doi: 10.1021/jo4020547 contributor: fullname: Liu, Y – volume: 22 start-page: 14342 year: 2016 ident: WOS:000384698200031 article-title: Beyond Chemoselectivity: Catalytic Site-Selective Aldolization of Diketones and Exploitation for Enantioselective Alzheimer's Drug Candidate Synthesis publication-title: CHEMISTRY-A EUROPEAN JOURNAL doi: 10.1002/chem.201602900 contributor: fullname: Nugent, TC – volume: 11 start-page: 1003 year: 2020 ident: WOS:000571976500009 article-title: Recent developments of small molecule gamma-secretase modulators for Alzheimer's disease publication-title: RSC MEDICINAL CHEMISTRY doi: 10.1039/d0md00196a contributor: fullname: Mekala, S – volume: 148 start-page: 436 year: 2018 ident: WOS:000428824700035 article-title: Secretase inhibitors for the treatment of Alzheimer's disease: Long road ahead publication-title: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1016/j.ejmech.2018.02.035 contributor: fullname: Kumar, D – volume: 71 start-page: 6859 year: 2006 ident: WOS:000240020100020 article-title: Reversal of diastereofacial selectivity in hydride reductions of N-tert-butanesulfinyl imines publication-title: JOURNAL OF ORGANIC CHEMISTRY doi: 10.1021/jo0609834 contributor: fullname: Colyer, JT – volume: 140 start-page: 2024 year: 2018 ident: WOS:000425475300011 article-title: Asymmetric Synthesis of Chiral Primary Amines by Ruthenium-Catalyzed Direct Reductive Amination of Alkyl Aryl Ketones with Ammonium Salts and Molecular H-2 publication-title: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY doi: 10.1021/jacs.7b12898 contributor: fullname: Tan, XF – volume: 20 start-page: 1306 year: 2010 ident: WOS:000273783800116 article-title: Piperidine-derived gamma-secretase modulators publication-title: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS doi: 10.1016/j.bmcl.2009.08.072 contributor: fullname: Hall, A – volume: 35 start-page: 984 year: 2002 ident: WOS:000179410200008 article-title: N-tert-Butanesulfinyl imines: Versatile intermediates for the asymmetric synthesis of amines publication-title: ACCOUNTS OF CHEMICAL RESEARCH contributor: fullname: Ellman, JA – volume: 57 start-page: 16152 year: 2018 ident: WOS:000452235600035 article-title: A Desymmetrization-Based Total Synthesis of Reserpine publication-title: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION doi: 10.1002/anie.201810974 contributor: fullname: Park, J – volume: 19 start-page: 5783 year: 2017 ident: WOS:000414723900018 article-title: Enantio- and Diastereoselective Organocatalytic Conjugate Additions of Nitroalkanes to Enone Diesters publication-title: ORGANIC LETTERS doi: 10.1021/acs.orglett.7b02735 contributor: fullname: Horwitz, MA – year: 2006 ident: 000716778300099.3 publication-title: Piperidines and related compounds for treatment of Alzheimer ' s disease – ident: ref3/cit3 doi: 10.1002/chem.201602900 – ident: ref2/cit2c doi: 10.1016/j.bmcl.2009.08.072 – ident: ref2/cit2b – ident: ref4/cit4b doi: 10.1021/jo4020547 – ident: ref4/cit4d doi: 10.1002/anie.201810974 – ident: ref1/cit1a doi: 10.1016/j.ejmech.2018.02.035 – ident: ref1/cit1b doi: 10.1039/D0MD00196A – ident: ref5/cit5 doi: 10.1021/jacs.7b12898 – ident: ref2/cit2a – ident: ref4/cit4a doi: 10.1002/ejoc.201601481 – ident: ref9/cit9 doi: 10.1002/asia.201402865 – ident: ref7/cit7 doi: 10.1021/jo0609834 – ident: ref4/cit4c doi: 10.1021/acs.orglett.7b02735 – ident: ref6/cit6 doi: 10.1021/ar020066u |
| SSID | ssj0000555 |
| Score | 2.4335868 |
| Snippet | A desymmetrization-based approach for the synthesis of piperidinyl acetic acid γ-secretase modulators has been developed. The synthetic sequence features the... A desymmetrization-based approach for the synthesis of piperidinyl acetic acid gamma-secretase modulators has been developed. The synthetic sequence features... |
| Source | Web of Science |
| SourceID | proquest crossref pubmed webofscience acs |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 15481 |
| SubjectTerms | Acetic Acid Amyloid Precursor Protein Secretases Chemistry Chemistry, Organic Gamma Secretase Inhibitors and Modulators Physical Sciences Science & Technology |
| Title | A Local Desymmetrization Approach to Piperidinyl Acetic Acid γ‑Secretase Modulators |
| URI | http://dx.doi.org/10.1021/acs.joc.1c01970 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestApp=WOS&DestLinkType=FullRecord&UT=000716778300099 https://www.ncbi.nlm.nih.gov/pubmed/34641679 https://search.proquest.com/docview/2581822787 |
| Volume | 86 |
| WOS | 000716778300099 |
| WOSCitedRecordID | wos000716778300099 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3LTuMwFLUQLGDDcwbKSx6JBZuU-Jl2WVVUCAEaiYfYRY7tSAyiQSRdwIpf4Fv4Dz6CL-HeJG2BDoJNIjnWVexr5xzn2ucSsqNDJ7kRImCpSwKZWBEkjNvAGYXb_4wVpWT-8Yk-OJeHl-pyLBb9OYLP2Z6xefNfZpvMAhuJYHU-wyOYGsiCuqfjj65SaiQMzrUYqfhMGEAYsvlHGJrglv-FoRJyegvVZq28VCrEnSbXzUGRNO3DpI7j961ZJPM18aSdaqQskSnfXyaz3WG-txVy0aFHCGwUlqL3NzeYaas6okk7te44LTL69wqlkQHw7sGWxROQcLty9OX59fHpFDloAbhIjzOHecGyu_wXOe_tn3UPgjrrQgAuE0UAfAxVAUPtbVs7aXyinG5zuKrUtFpQBKQtjLyXMgqZSWHBJH2aAtDbNrc6Eb_JdD_r-zVCVRJagYFaZ73UzLTAmNeOeSNa2ivTIDvQH3E9a_K4DIhzFleFNq47qUF2h76KbysNjq-r_hn6Mobuw-CH6ftskMdcATXBc79Rg6xWTh4ZE1JLDEfB-7z3-uh5ScRQaU-UjLpB2E-qdWuRdRQXKNZ_1tQNMsdx0wz-t1abZLq4G_gtYD1Fsl2O9zc-X_wx |
| link.rule.ids | 315,783,787,2772,27088,27936,27937,57066,57116 |
| linkProvider | American Chemical Society |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3NTtwwEB4heoALpS3Qhf4YiUMvWeL4J7vH1apo2-6iVvyIW-TYjkQrNohkD3DiFfosfY8-RJ-kM0k20AISXBLJsUa2J873OeP5DLCjQycjI0TAM5cGMrUiSHlkA2cUbf8zVlSS-ZN9PTqSn0_UyQKE81wYbESBlooqiH-jLsB3qex7brvcIimJcZH-TMUIl0SGhgc3316lVKsPHmnRivncMUBoZIt_0egOxbwXjSrk2XsO39o2VxtOfnRnZdq1V__JOT6lU6uw0tBQNqjfmxew4KcvYWk4P_3tFRwP2JhgjuHC9PLsjM7dqhM22aBRIWdlzr6eklAywt8l2rKUD4m3U8d-__pz_fOAGGmJKMkmuaNTwvKLYg2O9j4eDkdBcwZDgA4UZYDsjDQCQ-1tXztpfKqc7kd4VZnp9bAIKVwYey9lHHKT4fJJ-ixD2Lf9yOpUrMPiNJ_618BUGlpBYVtnvdTc9NCY1457I3raK9OBHRyPpJlDRVKFxyOe1IU2aQapAx_mLkvOa0WOh6tuz12a4PBRKMRMfT4rkkghUaEs4LgDG7WvW2NCaknBKWzPbee3zytaRrp7ouLXHeCPqTZsJNdJaqDcfFxX38PS6HAyTsaf9r9swXJE22noj7Z6A4vlxcy_RT5Upu-qKfAX240EpQ |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3NTtwwEB4hKtFe2tIfui1QV-LQS7Zx_JPd42rLCiggJLoVt8ixHYlWbBDJHuiJV-BZ-h59iD4JM042_aGV6CWRnGhke-x8nzOezwBbOnYyMUJEvHB5JHMropwnNnJG0fY_Y0WQzD841DtTuXeiTtqkMMqFwUpUaKkKQXya1eeuaBUG-Dsq_1zaPrdITFJcqN9TKQ_B2dH4-Of3VynVaYQnWnSCPrcMECLZ6ndEukUz_4pIAX0mj2Da1TtsOvnSn9d53379Q9Lxfxv2GB62dJSNmvGzCkt-9gTujxenwD2FTyO2T3DHcIF6eXZG5281iZts1KqRs7pkR6ckmIwweIm2LOVF4u3Use_fflxdHxMzrREt2UHp6LSw8qJ6BtPJ9sfxTtSexRChI0UdIUsjrcBYezvUThqfK6eHCV5VYQYDLEIqF6feS5nG3BS4jJK-KBD-7TCxOhfPYXlWzvwLYCqPraDwrbNeam4GaMxrx70RA-2V6cEW9kfWzqUqC2HyhGdNoc3aTurB24XbsvNGmePfr75ZuDXD7qOQiJn5cl5liULCQtnAaQ_WGn93xoTUkoJUWJ9fB0D3PNAz0t8TgWf3gN_ltXErvU6SA_XLuzX1NawcvZ9k-7uHH17Bg4R21dCPbbUOy_XF3G8gLarzzTALbgAysgcf |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Local+Desymmetrization+Approach+to+Piperidinyl+Acetic+Acid+%CE%B3-Secretase+Modulators&rft.jtitle=Journal+of+organic+chemistry&rft.au=Cheng%2C+Peng&rft.au=Lu%2C+Haigen&rft.au=Zu%2C+Liansuo&rft.date=2021-11-05&rft.issn=0022-3263&rft.eissn=1520-6904&rft.volume=86&rft.issue=21&rft.spage=15481&rft.epage=15487&rft_id=info:doi/10.1021%2Facs.joc.1c01970&rft.externalDBID=n%2Fa&rft.externalDocID=10_1021_acs_joc_1c01970 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-3263&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-3263&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-3263&client=summon |