Reduction of some mesyloxy and tosyloxy steroids with sodium iodide and zinc dust

Kočovský, Pavel; Černý, V.

doi:10.1135/cccc19790246

Cited by 19 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compound 11 was synthesized in a four-step reaction sequence, using (4 R ,5 R )-4-(4-chlorophenyl)-5-hydroxy-2-piperidone ( 18 ) as the starting material. Removal of the hydroxy group of 18 , which is the key step of the sequence, was unsuccessfully attempted using a variety of reductive substitution reactions, based on zinc as the reducing agent, , or using platinum-catalyzed hydrogenation conditions . Subsequently, deoxygenation at C-5 of 18 was attempted using Barton−McCombie reaction conditions.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Pharmacology of the Baclofen Homologues 5-Amino-4-(4-chlorophenyl)pentanoic Acid and theR- andS-Enantiomers of 5-Amino-3-(4-chlorophenyl)pentanoic Acid

Karla¹,

Ebert²,

Thorkildsen³

et al. 1999

J. Med. Chem.

View full text Add to dashboard Cite

(RS)-5-Amino-4-(4-chlorophenyl)pentanoic acid (10) and the R-form (11) and S-form (12) of (RS)-5-amino-3-(4-chlorophenyl)pentanoic acid, which are homologues of the 4-aminobutanoic acidB (GABAB) receptor agonist (RS)-4-amino-3-(4-chlorophenyl)butanoic acid (baclofen), were synthesized. Compound 10 was synthesized by homologation at the carboxyl end of baclofen using a seven-step reaction sequence. N-Boc-protected (4R, 5R)-4-(4-chlorophenyl)-5-hydroxy-2-piperidone (18) was deoxygenated via a modified Barton-McCombie reaction to give N-Boc-protected (R)-4-(4-chlorophenyl)-2-piperidone (20), which was ring opened and deprotected to give 11.HCl. The corresponding S-enantiomer, 12.HCl, was synthesized analogously from the 4S,5S-enantiomer of 18, compound 21. The enantiomeric purities of 11.HCl (ee = 99.8%) and 12. HCl (ee = 99.3%) were determined by chiral HPLC. Compound 10 did not show detectable affinity for GABAA or GABAB receptor sites and was inactive as an agonist or an antagonist at GABAB receptors in the guinea pig ileum. Like the enantiomers of baclofen, neither 11 nor 12 showed detectable affinity for GABAA receptor sites, and in agreement with the findings for (S)-baclofen, 12 did not interact significantly with GABAB receptor sites. Compound 11 (IC50 = 7.4 +/- 0.6 microM), a homologue of (R)-baclofen (2), was shown to be some 50 times weaker than 2 (IC50 = 0.14 +/- 0.01 microM) as an inhibitor of GABAB binding. Accordingly, 11 (EC50 = 150 +/- 23 microM) was shown to be weaker than 2 (EC50 = 11 +/- 1 microM) as an inhibitor of electrically induced contractions of the guinea pig ileum. However, whereas this effect of 2 was sensitive to the GABAB antagonist, CGP35348 (4), the inhibition by 11 was not significantly affected. Furthermore, 12 (EC50 = 310 +/- 16 microM) was shown to be one-half as potent as 11 in this test system, and this effect of 12 also was insensitive to 4. The dissimilarities of the pharmacological effects of 2 and compounds 11 and 12 were emphasized by the observation that whereas 2 only inhibits the ileum contraction by 59 +/- 5%, 11 as well as 12 were shown to inhibit this response by approximately 94%. Neither 11 nor 12 appeared to affect significantly cholinergic mechanisms in the ileum, and their mechanism(s) of action remain enigmatic.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis and Pharmacology of the Baclofen Homologues 5-Amino-4-(4-chlorophenyl)pentanoic Acid and theR- andS-Enantiomers of 5-Amino-3-(4-chlorophenyl)pentanoic Acid

Karla¹,

Ebert²,

Thorkildsen³

et al. 1999

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…Thus, treatment of 25 with LiOH in THF:MeOH:H 2 O furnished a mixture of 26 and 8 (93 % yield) in which the desired hydroxy acid 26 predominated ( 26 : 8 ca 2:1, chromatographically separated). The required aldehyde 29 (anti C1/C2) was then synthesized from hydroxy acid 26 through a sequence involving selective methylation of the carboxylic acid moiety (K 2 CO 3 , MeI, 85 % yield), mesylation of the hydroxy group (MsCl, Et 3 N, 90 % yield), and reduction of the resulting mesylate methyl ester with Zn dust33 in the presence of NaI to afford tetramethylated decalin system 28 (83 % yield). The methyl ester of the latter was then reduced (DIBAL, 93 % yield) and the resulting alcohol was oxidized (DMP, 87 % yield) to afford the desired aldehyde 29 as shown in Scheme .…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis and Structural Revision of Antibiotic CJ‐16,264

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In Scheme , we show the synthetic approach that was used to prepare 25-OH′ starting from 25-hydroxycholesterol (25-OH). In brief, regioselective tosylation of the C-3 hydroxyl group of 25-OH, followed by reduction with Zn and NaI in DME/H 2 O afforded the requisite “upside down” isomer, 25-OH′. − …”

mentioning

confidence: 95%

“…In brief, regioselective tosylation of the C-3 hydroxyl group of 25-OH, followed by reduction with Zn and NaI in DME/H 2 O afforded the requisite “upside down” isomer, 25-OH’ 8-10…”

mentioning

confidence: 99%

An Upside Down View of Cholesterol’s Condensing Effect: Does Surface Occupancy Play a Role?

et al. 2010

View full text Add to dashboard Cite

The condensing action of cholesterol has been compared with that of a structural isomer having its hydroxyl group located at the C-25 position (i.e., 25-OH'); that is, an isomer favoring an "upside down" orientation in lipid membranes. Surface pressure-area isotherms of mixed monolayers made from 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/cholesterol and DMPC/25-OH' have established that 25-OH' has a weaker condensing effect than cholesterol. Nearest-neighbor recognition measurements in liposomes made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) have also shown that 25-OH' has a weaker condensing effect in the physiologicallyrelevant fluid bilayer state. These findings provide support for surface occupancy playing a role in the condensing action of cholesterol.The role that cholesterol plays in controlling the conformation and function of integral membrane proteins as well as lipids in cell membranes continues to be a subject of considerable interest. 1,2 Studies with model membranes have already shown that certain high-melting phospholipids can combine with cholesterol to form "condensed complexes" as well as a "liquid-ordered" phase. 3,4 Although the ability of cholesterol to condense fluid phospholipids was demonstrated more than 80 years ago, the mechanism of its condensing action remains to be established. 5 One model that has been proposed (i.e., the "umbrella model") considers that both acyl chains of a phospholipid and a neighboring cholesterol molecule are required to share limited space beneath the phospholipid's head group, and that the hydrophobic nature of cholesterol forces it together with these acyl chains. 6 Alternatively, with the "template model", the flexible acyl chains of the phospholipid are able to complement, perfectly, the planar nucleus of a neighboring cholesterol molecule, resulting in a high number of hydrophobic contacts and tight packing. 7 In both of these models, hydrophobic interactions have been proposed to play a major role.In the present study, we have tested whether surface occupancy plays a role in cholesterol's condensing action. We define "surface occupancy" as the taking up of space in the interphase region of phospholipid membranes; that is, the region where water makes direct contact with exposed CH 2 groups. Since phospholipid head groups occupy only about half of the surface area of liquid phospholipid bilayers, the remaining surface is occupied by partially hydrated CH 2 groups. In principle, by replacing the space occupied by these wet CH 2 groups, the sterol nucleus of cholesterol should release them into the hydrophobic interior of the membrane, resulting in a partial straightening of the acyl chains, stronger chain-chain interactions and tighter packing.AUTHOR EMAIL ADDRESS (slr0@lehigh.edu). SUPPORTING INFORMATION. Experimental procedures and tables of data. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public Access Author ManuscriptLangmuir. Author manuscript; available in PMC 2011 April 20....

show abstract

Reduction of some mesyloxy and tosyloxy steroids with sodium iodide and zinc dust

Cited by 19 publications

References 0 publications

Synthesis and Pharmacology of the Baclofen Homologues 5-Amino-4-(4-chlorophenyl)pentanoic Acid and theR- andS-Enantiomers of 5-Amino-3-(4-chlorophenyl)pentanoic Acid

Synthesis and Pharmacology of the Baclofen Homologues 5-Amino-4-(4-chlorophenyl)pentanoic Acid and theR- andS-Enantiomers of 5-Amino-3-(4-chlorophenyl)pentanoic Acid

Total Synthesis and Structural Revision of Antibiotic CJ‐16,264

An Upside Down View of Cholesterol’s Condensing Effect: Does Surface Occupancy Play a Role?

Contact Info

Product

Resources

About