cas 203866-13-1, N-BOC-cis-4-fluoro-L-proline

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Large-Scale Practical Synthesis of Boc-Protected 4-Fluoro-l-Proline
A large-scale synthesis process of N-Boc-4-fluoro-l-proline (1) from N-Boc-4-hydroxy-l-proline methyl ester (2) using nosyl fluoride (13) as a deoxyfluorinating agent has been developed. An eco-friendly and large-scale feasible process using a single solvent was developed to afford moderate yields of products with excellent purity >99% by high-performance liquid chromatography. The key feature of the optimization involving chromatography-free purification and isolation on a kilogram-scale at a pilot plant scale is described.
Kashid, Bharat,Merwade, Arvind Y,Rafeeq, Mohammad,Tamboli, Yasinalli,Yadav, Ram Prasad
p. 1609 - 1613
(2020)
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West request acid bei geleg sandbank and intermediate preparation method
The invention relates to a preparation method of besigliptin and its intermediate, and concretely relates to a preparation method of an azadicyclic compound besigliptin and its key intermediate. The preparation method comprises the following steps: carrying out step a, step b and step c to prepare the key intermediate compound of formula VII, carryin gout isomer resolution and protective group removal on the compound of formula VII to obtain a compound of formula XV, coupling the compound of formula XV with the compound of formula XIII, and salifying to form a target compound I. The preparation method has the advantages of substantial reduction of the production cost, simple production flow, yield increase, and suitableness for industrial production.
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Paragraph 0100-0104

(2019/02/26)

Design and synthesis of galactose-conjugated fluorinated and non-fluorinated proline oligomers: Towards antifreeze molecules
Galactose-conjugated fluorinated and non-fluorinated proline oligomers that exhibit an α-helical structure with hydrophilic and lipophilic parts were designed as potential antifreeze molecules. These galactose-proline oligomers were synthesized and their physical properties were evaluated. Interestingly, the non-fluorinated galactose-proline oligomers showed in contrast to the fluorinated analogues weak antifreeze activity. The difference in antifreeze activity should be attributed to the fluorine gauche effect, which should induce a conformation in fluorinated prolines that is different from that of natural proline. The results obtained in this study thus suggest that the 3D conformation of the galactose-conjugated fluorinated and non-fluorinated proline oligomers is very important for their anti-freezing properties.
Sumii, Yuji,Hibino, Hayata,Saidalimu, Ibrayim,Kawahara, Hidehisa,Shibata, Norio
p. 9749 - 9752
(2018/09/10)

As hepatitis c inhibitor spiro compound and its use in medicine
The invention provides a spiro compound serving as a hepatitis c inhibitor and application thereof in a medicine. The compound is a compound as shown in a formula (I) or a stereisomer, a geometric isomer, a tautomer, nitric oxide, an aquo-complex, a solvate, a metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in the formula (I). The invention also provides a pharmaceutical composition containing the compound, application of the compound and the pharmaceutical composition in inhibition of HCV (Hepatitis C Virus) copy and HCV virus protein, as well as the application of the compound and the pharmaceutical composition in prevention, handling, treatment or relieving of HCV infection or hepatitis c disease for a patient. The formula I is as shown in the specification.
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(2017/12/28)

Bridged Ring compounds As Hepatitis C Virus (HCV) Inhibitors And Pharmaceutical Applications Thereof
Provided herein is a compound having Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are pharmaceutical compositions comprising the compounds disclosed herein, which can be used for treating HCV infection or a HCV disorder.
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(2015/03/28)

BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS (HCV) INHIBITORS AND PHARMACEUTICAL APPLICATIONS THEREOF
Provided herein is a compound having Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are pharmaceutical compositions comprising the compounds disclosed herein, which can be used for treating HCV infection or a HCV disorder.
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(2014/02/16)

FUSED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
Provided are fused tricyclic compounds effective to inhibit the function of the NS5A protein of formula (I), wherein X, X', Y, Y', A, A',Q1, Q2, R1-R4, X4, R5a, f and W are defined as in the description. Also provided herein are pharmaceutical compositions thereof, and uses in the manufacture of a medicament for treating HCV infection or a HCV disorder thereof.
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(2014/06/23)

SPIRO RING COMPOUND AS HEPATITIS C VIRUS (HCV) INHIBITOR AND USES THEREOF FIELD OF THE INVENTION
A compound of formula (I) or a stereoisomer, a geometric isomer. a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof is provided, which can be used for treating HCV infection or a HCV disorder. Also a pharmaceutical composition comprising the compound and the use of the compound and the pharmaceutical composition thereof are provided, which can also be used for treating HCV infection or a HCV disorder.
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(2014/06/23)

Design, synthesis and biological evaluation of hetero-aromatic moieties substituted pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors
A series of novel hetero-aromatic moieties substituted α-amino pyrrole-2-carbonitrile derivatives was designed and synthesized based on structure-activity relationships (SARs) of pyrrole-2-carbonitrile inhibitors. All compounds demonstrated good dipeptidyl peptidase IV (DPP4) inhibitory activities (IC50 = 0.004-113.6 μM). Moreover, compounds 6h (IC50 = 0.004 μM) and 6n (IC50 = 0.01 μM) showed excellent inhibitory activities against DPP4, good selectivity (compound 6h, selective ratio: DPP8/DPP4 = 450.0; DPP9/DPP4 = 375.0; compound 6n, selective ratio: DPP8/DPP4 = 470.0; DPP9/DPP4 = 750.0) and good efficacy in an oral glucose tolerance test in ICR mice. Furthermore, compounds 6h and 6n demonstrated moderate PK properties (compound 6h, F% = 37.8%, t1/2 = 1.45 h; compound 6n, F% = 16.8%, t1/2 = 3.64 h).
Ji, Xun,Su, Mingbo,Wang, Jiang,Deng, Guanghui,Deng, Sisi,Li, Zeng,Tang, Chunlan,Li, Jingya,Li, Jia,Zhao, Linxiang,Jiang, Hualiang,Liu, Hong
p. 111 - 122
(2014/03/21)

Design, synthesis and biological evaluation of 4-fluoropyrrolidine-2- carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors
Based on the previous work in our group and the principle of computer-aided drug design, a series of novel β-amino pyrrole-2-carbonitrile derivatives was designed and synthesized. Compounds 8l and 9l were efficacious and selective DPP4 inhibitors resulting in decreased blood glucose in vivo. Compound 8l had moderate DPP4 inhibitory activity (IC50 = 0.05 μM) and good oral bioavailability (F = 53.2%). Compound 9l showed excellent DPP4 inhibitory activity (IC50 = 0.01 μM), good selectivity (selective ratio: DPP8/DPP4 = 898.00; DPP9/DPP4 = 566.00) against related peptidases, and good efficacy in an oral glucose tolerance tests in ICR mice and moderate PK profiles (F = 22.8%, t1/2 = 2.74 h). Moreover, compound 9l did not block hERG channel and exhibited no inhibition of liver metabolic enzymes such as CYP2C9.
Li, Jia,Ji, Xun,Xia, Chunmei,Wang, Jiang,Su, Mingbo,Zhang, Lei,Dong, Tiancheng,Li, Zeng,Wan, Xia,Li, Jingya,Zhao, Linxiang,Gao, Zhaobing,Jiang, Hualiang,Liu, Hong
p. 242 - 256
(2014/09/29)

BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
Provided herein is a compound of formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are a pharmaceutical composition comprising the compound and the use of the compound and the pharmaceutical composition thereof, which can also be used for treating HCV infection or a HCV disorder.
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(2014/09/16)

Synthesis and biological evaluation of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives as dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes
A novel series of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2- carbonitrile derivatives was designed, synthesized, and found to act as dipeptidyl peptidase-4 (DPP-4) inhibitors. From this series of compounds, compound 17a was identified as an efficacious, safe, and selective inhibitor of DPP-4. In vivo studies in ICR and KKAy mice showed that administration of this compound resulted in decreased blood glucose in these mice after an oral glucose challenge. Compound 17a showed high DPP-4 inhibitory activity (IC50 = 0.017 μM), moderate selectivity against DPP-4 (selective ratio: DPP-8/DPP-4 = 1324; DPP-9/DPP-4 = 1164), and good efficacy in oral glucose tolerance tests in ICR and KKAy mice. These in vivo anti-diabetic properties and its desirable pharmacokinetic profile in Sprague-Dawley rats demonstrate that compound 17a is a promising candidate for development as an anti-diabetic agent.
Wang, Jiang,Feng, Ying,Ji, Xun,Deng, Guanghui,Leng, Ying,Liu, Hong
p. 7418 - 7429
(2013/11/19)

OXADIAZOLE COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
The invention provides novel beta-secretase inhibitors and methods for their including methods of treating Alzheimer's disease.
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(2012/05/05)

Incorporation of fluoroprolines to proctolin: Study on the effect of a fluorine atom toward peptidic conformation
In spite of quite small steric perturbation, substitution of proline (Pro) in the target pentapeptide proctolin (Arg-Tyr-Leu-Pro-Thr) for (4R)- as well as (4S)-4-fluoroproline led to apparent alteration of the pyrrolidine ring structure which eventually r
Kitamoto, Takamasa,Ozawa, Taeko,Abe, Megumi,Marubayashi, Shunsuke,Yamazaki, Takashi
p. 286 - 293
(2008/12/22)

NOVEL DIPEPTIDYL PEPTIDASE-IV INHIBITORS
The present invention relates to novel compounds exhibiting excellent inhibitory activity versus Dipeptidyl Peptidase-IV (DPP-IV), methods of preparing the same and pharmaceutical compositions containing the same as an active agent.
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Page/Page column 41

(2008/12/07)

1,3-Dihydro-2H-Indole-2-One Compound and Pyrrolidine-2-One Compound Fused With Aromatic Heterocycle
It is intended to provide a drug which is efficacious against pathological conditions relating to arginine-vasopressin V1b receptor. More particularly speaking, it is intended to provide a drug which has a therapeutic or preventive effect on depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, hypertension, digestive diseases, drug addiction, epilepsy, brain infarction, brain ischemia, brain edema, head injury, inflammation, immune diseases, alopecia and so on. As the results of intensive studies, a novel 1,3-dihydro-2H-indol-2-one compound and a pyrrolidin-2-one compound fused with a heteroaromatic ring, which are highly selective antagonists of arginine-vasopressin V1b receptor, have high metabolic stabilities and show favorable brain penetration and high plasma concentrations, are found, thereby achieving the above objective.
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Page/Page column 59

(2009/01/24)

VLA-4 INHIBITOR
An object of the present invention is to provide a compound which selectively inhibits binding of a ligand and ±421 integrin (VLA-4), a process for producing the compound, and a medicament containing the compound. A compound represented by the formula (I) etc. orasaltthereof, a process for producing the compound or a salt thereof, a medicament containing the compound or a salt thereof, as well as a preventive and/or a therapeutic agent for a disease caused by cell adhesion, for example, inflammatory reaction, autoimmune disease, cancer metastasis, bronchial asthma, nasal obstruction, diabetes, arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease and rejection reaction at transplantation, containing the compound or a salt thereof as a primary component. [wherein Y 1 represents a divalent aryl group etc. , V 1 represents an aryl group etc., and R 11 to R 14 represent H, OH or a halogen atom etc.]
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(2008/06/13)

Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: Oxadiazolyl ketones
Synthesis of a novel series of DPPIV inhibitors with 1,2,4- and 1,3,4-oxadiazolyl ketone derivatives and its structure-activity relationships are discussed. Compound 18h showed good inhibitory activity against DPPIV and favorable pharmacokinetic properties. In vivo pharmacodynamic efficacy and co-crystal structure of compound 18h with DPPIV is also described.
Koo, Ki Dong,Kim, Min Jung,Kim, Sungsub,Kim, Kyoung-Hee,Hong, Sang Yong,Hur, Gwong-Cheung,Yim, Hyeon Joo,Kim, Geun Tae,Han, Hee Oon,Kwon, O Hwan,Kwon, Tae Sik,Koh, Jong Sung,Lee, Chang-Seok
p. 4167 - 4172
(2008/02/09)

NOVEL DIPEPTIDYL PEPTIDASE INHIBITORS AND PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
The present invention relates to novel compounds representated by formula (I), where R, R1, R2, R3, X, Y, m, n are as defined.The present invention relates to compounds of the general formula I their derivatives, their analogs, their tautomeric forms, their stereoisomers, their diastereomers, their bioisosteres, their polymorphs, their pharmaceutically acceptable salts and pharmaceutically acceptable compositions containing them which are predominantly dipeptidyl peptidase IV inhibitors. The present invention also relates to the processes for the preparation of novel compounds of formula (I) and their use in treating type II diabetes and diabetic complications thereof and also for treating dislipidemia, hypercholesterolemia, obesity and hyperglycemia.
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Page/Page column 61

(2008/06/13)

METHOD FOR PRODUCING FLUORINATED PROLINE DERIVATIVE
Disclosed is a method for efficiently producing a high-purity fluorinated proline derivative with high yield. Specifically disclosed is a method for producing a compound represented by the general formula (2) below wherein a compound represented by the formula (1) below is reacted with a fluorination agent, and then chlorine, bromine, iodine, hypochlorous acid, hypochlorite, hypobromous acid, hypobromite or N-halogenosuccinimide is caused to act on the reaction product obtained by the preceding reaction and containing the compound represented by the general formula (2) below and a by-product for chemically changing the by-product. (1) (In the formula (1), R1 represents an unsubstituted or substituted alkyl group having 1-6 carbon atoms or the like; R2 represents an unsubstituted or substituted alkyl group having 1-6 carbon atoms or the like; and R3 represents a hydroxyl group or the like.) (2) (In the formula (2), R1 and R2 are as defined above.)
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Page/Page column 38-40

(2008/06/13)

Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists
A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12 ml/min/kg and 11p, 9 ml/min/kg).
Chiba, Jun,Takayama, Gensuke,Takashi, Tohru,Yokoyama, Mika,Nakayama, Atsushi,Baldwin, John J.,McDonald, Edward,Moriarty, Kevin J.,Sarko, Christopher R.,Saionz, Kurt W.,Swanson, Robert,Hussain, Zahid,Wong, Angela,MacHinaga, Nobuo
p. 2725 - 2746
(2007/10/03)

1,3-DIHYDRO-2H-INDOL-2-ONE DERIVATIVE
A 1,3-dihydro-2H-indol-2-one derivative expressed by Formula 1 (wherein R1 is a halogen atom, a C1 to C4 alkyl group, etc., and R2 is a hydrogen atom, a halogen atom, etc., or R2 is in the 6-position of the indol-2-one and R1 and R2 join together to form a C3 to C6 alkylene group, R3 is a halogen atom, a hydroxyl group, etc., and R4 is a hydrogen atom, a halogen atom, a C1 to C4 alkyl group, etc., or R4 is in the 3-position of the phenyl and R3 and R4 join together to form a methylenedioxy group, R5 is a hydrogen atom or a fluorine atom, R6 is an ethylamino group, a dimethylamino group, etc., R7 is a C1 to C4 alkoxy group, and R8 is a C1 to C4 alkoxy group), or a pharmaceutically acceptable salt of this derivative. This is a novel compound that has antagonistic activity against an aruginine-vasopressin V1b receptor.
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Page/Page column 18

(2008/06/13)

PROCESS FOR PRODUCTION OF CIS-4-FLUORO-L-PROLINE DERIVATIVES
The present invention provides a safer method for production of a cis-4-fluoro-L-proline derivative under milder conditions and in good yield to give a product of high purity on an industrial scale at low cost. Namely, the present invention provides a method for producing a cis-4-fluoro-L-proline derivative, which comprises reacting a trans-4-hydroxy-L-proline derivative of the following Formula [I]: (wherein R1 represents a protecting group for an α-amino group, and R2 represents a protecting group for a carboxyl group) with N,N-diethyl-N-(1,1,2,3,3,3-hexafluoropropyl)amine in the presence of a hydrogen fluoride-scavenger.
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Page/Page column 7

(2008/06/13)

VLA-4 INHIBITOR
A compound which selectively inhibits bonding between a ligand and α4β1 integrin (VLA-4); a process for producing the compound; and a medicine containing the compound. The compound is one represented by, e.g., the formula (I) or a salt thereof. Also provided is a preventive and/or therapeutic agent which contains the compound or salt as a major component and is effective against diseases attributable to cell adhesion, such as, e.g., inflammatory reaction, autoimmune disease, cancer metastasis, bronchial asthma, nasal obstruction, diabetes, arthritis, psoriasis, multiple sclerosis, inflammatory intestinal disease, and rejection reaction in transplantation. (In the formula, Y1 represents arylene, etc.; V1 represents aryl, etc.; and R11 to R14 each represents H, OH, halogeno, etc.)
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(2010/02/15)

Collagen mimics
A novel collagen mimic comprising a tripeptide unit having the formula (flpYaaGly)n, where flp is 4(S)-fluoro-L-proline, is disclosed. The collagen mimic has increased stability relative to the collagen-related triple helices (ProYaaGly)n
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(2008/06/13)

2-CYANOPYRROLIDINECARBOXAMIDE COMPOUND
A compound of the formula (I) or a pharmaceutically acceptable salt thereof: [wherein X1 and X2 each is independently lower alkylene; X3 is =CH2, =CHF or =CF2; R1 is substituent, R2 and R3 each is independently H or lower alkyl; n is 0, 1, 2, 3 or 4.] having the activity inhibiting DPP-IV activity. They are therefore useful in the treatment of conditions mediated by DPP-IV, such as NIDDM.
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Page/Page column 55-56

(2008/06/13)

2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV
We report the synthesis and biological activity of a series of 2-cyano-4-fluoro-1-thiovalylpyrrolidine inhibitors of DPP-IV. Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog.
Haffner, Curt D.,McDougald, Darryl L.,Reister, Steven M.,Thompson, Brian D.,Conlee, Christopher,Fang, Jing,Bass, Jonathan,Lenhard, James M.,Croom, Dallas,Secosky-Chang, Melissa B.,Tomaszek, Thaddeus,McConn, Donavon,Wells-Knecht, Kevin,Johnson, Paul R.
p. 5257 - 5261
(2008/12/23)

2-CYANOPYRROLIDINE DERIVATIVES AND THEIR USE AS DPP-IV INHIBITORS
A compound of the formula (I) or a pharmaceutically acceptable salt thereof: [wherein X is CFH, or CF?2#191, R?1? is the moiety represented by the formula: [wherein R?2? is (lower) alkyl, R?3? is phenyl-(lower)alkyl, and the like.], and the like.] Compounds of formula (I) inhibit DPP-IV activity. They are therefore useful in the treatment of conditions mediated by DPP-IV, such as NIDDM.
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Page 24

(2010/02/09)

CYANOPYRROLIDINE DERIVATIVES
A cyanopyrrolidine derivative represented by Formula (1): [wherein R1 is a halogen atom, a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or an alkyl group having 1 to 5 carbon atoms, R2 is a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or an alkyl group having 1 to 5 carbon atoms, or R1 and R2 together form an oxo, a hydroxyimino group, an alkoxyimino group having 1 to 5 carbon atoms or an alkylidene group having 1 to 5 carbon atoms, ???R3 and R4 are each a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or an alkyl group having 1 to 5 carbon atoms, or R3 and R4 together form an oxo, a hydroxyimino group, an alkoxyimino group having 1 to 5 carbon atoms or an alkylidene group having 1 to 5 carbon atoms, ???X is an oxygen atom or a sulfur atom, ???Y is -CR5R6- (wherein R5 and R6 are the same or different, and are each a hydrogen atom, a halogen atom, an optionally substituted alkyl group having 1 to 10 carbon atoms or an optionally substituted alkenyl group having 2 to 10 carbon atoms), or -CR7R8-CR9R10- (wherein R7, R8, R9 and R10 are the same or different, and each a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 10 carbon atoms, or R7 and R9 together with the carbon atom to which they are attached form an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted cycloalkenyl group having 4 to 8 carbon atoms, an optionally substituted bicycloalkyl group having 5 to 10 carbon atoms, or an optionally substituted bicycloalkenyl group having 5 to 10 carbon atoms) and ???Z is a hydrogen atom or an optionally substituted alkyl group having 1 to 10 carbon atoms, or Y and Z together with the nitrogen atom to which they are attached form an optionally substituted cyclic amino group having 2 to 10 carbon atoms], or a pharmaceutically acceptable salt thereof.
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(2008/06/13)

Stereoelectronic effects on collagen stability: The dichotomy of 4-fluoroproline diastereomers
Collagen is the most abundant protein in animals. Natural collagen consists of a triple helix of (Xaa-Yaa-Gly)n chains, in which the Xaa and Yaa residues are often l-proline. Here, a (2S,4S)-4-fluoroproline (flp) residue is shown to be greatly stabilizing in the Xaa position (but destabilizing in the Yaa position). In contrast, a (2S,4R)-4-fluoroproline (Flp) residue is shown to be greatly destabilizing in the Xaa position (but stabilizing in the Yaa position). The dichotomous effect of the diastereomers appears to arise from a gauche effect, which alters pyrrolidine ring pucker and hence properly (or improperly) preorganizes main-chain dihedral angles. Thus, the rational use of stereoelectronic effects can enhance the conformational stability of a protein. Copyright
Hodgest, Jonathan A.,Raines, Ronald T.
p. 9262 - 9263
(2007/10/03)

Practical synthesis of Boc and Fmoc protected 4-fluoro and 4-difluoroprolines from trans-4-hydroxyproline
Boc-cis-4-fluoro-L-proline and 4-difluoro-L-proline, usable in classical peptide synthesis, were obtained in respectively 71% (3 steps) and 65% (4 steps) overall yields from the readily available trans-4-hydroxy-L-proline methyl ester. The corresponding fluorinated trans-isomer was isolated in 24% yield (5 steps). Transformation of Boc-protected compounds to their Fmoc-equivalents was performed in high yields.
Demange, Luc,Menez, Andre,Dugave, Christophe
p. 1169 - 1172
(2007/10/03)