CAS: 1482-97-9; H-Dap-Oh.Hcl

上下游产品

(S)-3-amino-2-tert-butoxycarbonylaminopropionic acid propionamide hydr°Chloride(2S)-3-amino-2-(tert-butoxycarbonyl)aminopropionamide hydr°Chloride 2)-CONH2B°C-Dap(NH2)-CONH2 (1'S,4S)-1-(1'-Phenyleth-1'-yl)-4-methoxycarbonylimidazolidin-2-one L-2-Amino-3-ureido-propanoic acid albizzine b-oxalylamino-L-alanine α-N-oxalyl-L-α,β-diaminopropionic acid

L-天门冬氨酸置于sodium Azide,硫酸体系中,用 氯仿 用作溶剂,化学反应 4.0H,以58%的收率获得l-2,3-二氨基丙酸盐酸盐
参考文献:Flexible And Convergent Total Synthesis Of Cyclotheonamide B
标题:Flexible And Convergent Total Synthesis Of Cyclotheonamide B
摘要:A Convergent Approach Using Two Key Intermediates,Segment A [a L-Proline-L-Alpha-Hydroxy-Beta-Homoarginine-D-Phenylalanine (Pro-Harg-D-Phe) Tripeptide] And Segment B [a Vinylogous L-Tyrosine-L-2,3-Diaminopropanoic Acid (Vtyr-Dpr) Dipeptide],Was Developed For The Synthesis Of Cyclotheonamide B (Scheme 1). The Starting Compound For The Preparation Of The Harg Moiety 7,The Predominant Part Of Segment A,Was N-Alpha-(Benzyloxycarbonyl)-N-Omega,N(Omega)'Bis(Tert-Butyloxycarbonyl)-L-Arginine Methyl Ester (15,Scheme 2),Which Was Converted Into The Aldehyde 16 And Subsequently Homologated Using [tris(Methylthio)Methyl]Lithium As A Carboxylic Acid Anion Equivalent. Coupling With Properly Protected Pro And D-Phe Derivatives Gave Smoothly The Desired Pro-Harg-D-Phe Tripeptide Derivative 24. The Key Feature Of Segment B,I.E.,The L-Tyrosine-Derived Alpha,Beta-Unsaturated Gamma-Amino Acid 4,Was Prepared By A Wadsworth-Emmons Olefination Of The Aldehyde 29 (Scheme 3) Derived From N-(Tert-Butyloxycarbonyl),O-Tert-Butyl-L-Tyrosine Methyl Ester (28). Selective N-(Tert-Butyloxycarbonyl) Removal In The Presence Of The Aryl Tert-Butyl Ether Present In The Fully Protected Segment B,I.E.,32,Was Achieved By Treatment With Trimethylsilyl Triflate/2,6-Lutidine To Give Vtyr-Dpr Dipeptide Derivative 34 In Quantitative Yield. Coupling Of The Key Intermediates 24 And 34 Using 2-(1H-Benzotriazol-L-yl)-1,1,3,3-Tetramethyluronium Tetrafluoroborate (Tbtu) Afforded The Protected Linear Pentapeptide 35 In High Yield (Scheme 4). Treatment Of 35 With Pd(Pph3)(4)/morpholine Resulted In Simultaneous Removal Of The C-Terminal Allyl Group And The N-Terminal Allyloxycarbonyl Group To Yield 36. Ring Closure Was Effected Under Dilution Conditions By Treatment With Tbtu/1-Hydroxybenzotriazole/4-(Dimethylamino And Gave The Protected Cyclopentapeptide 37 In 61% Yield. Oxidation Of The Hydroxyl Group With Dess-Rlartin Periodinane (24 H,40 Degrees C) In The Presence Of Tert-Butyl Alcohol Gave 38,Which Was Then Subjected To O,N-Deprotection With Trifluoroacetic Acid/thioanisole. Subsequent HPLC Purification Afforded Cyclotheonamide B In An Overall Yield Of 1.8% In 17 Steps.
Doi:10.1021/jo961447M

专利信息

专利号:US-12227528-B2
优先权日:2017-11-09
标 题:Glucose-sensitive albumin-binding derivatives
发明人：KRUSE THOMAS; KOFOD-HANSEN MIKAEL; MUENZEL MARTIN WERNER BORCHSENIUS; THOEGERSEN HENNING; SAUERBERG PER; EWALD JAKOB; BEHRENS CARSTEN; HOEG-JENSEN THOMAS; BALSANEK VOJTECH; DROBNAKOVA ZUZANA; DROZ LADISLAV; HAVRANEK MIROSLAV; KOTEK VLADISLAV; STENGL MILAN; SNAJDR IVAN; DRUSANOVA HANA
权利人:NOVO NORDISK AS
摘要:This invention relates to glucose-sensitive albumin-binding diboron conjugates. More particularly the invention provides novel diboron compounds, and in particular diboronate or diboroxole compounds, useful as intermediate compounds for the synthesis of diboron conjugates.

专利号:EP-4227313-B1
优先权日:2017-11-09
标题:1-hydroxy-4-(trifluoromethyl)-1,3-dihydrobenzo[c] [1,2]oxaborole-6-carboxylic acid and its use in the synthesis of glucose-sensitive albumin-binding derivatives