Cyclic Thiocarbonates Research Articles

Novel Synthon of N‐Boc‐Phytosphingosine‐3,4‐thiocarbonate for the Synthesis of Sphingosine Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Novel Synthon of N-Boc-Phytosphingosine-3,4-thiocarbonate for the Synthesis of Sphingosine Derivatives

Phytosphingosine, one of the major sphingosine derivatives was found in microorganisms, yeast, plants, and fungi as a major membrane component, and also found in many mammalian tissues and interestingly in some cancer celltypes. The roles of sphingosine derivatives have been enigmatic but they are recently proved to be essential in cell communications and regulation of cell growth. Sphingosine-1-phosphate, the most focused compound in sphingosine derivatives is known to affect fundamental cellular functions, it can also reduce mortality in hypoxic cardiac myocytes, and proved to be crucial in cancer development and progression. Much attention has also been paid to KRN7000, one of α-galactosylceramides as an interesting immunomodulator, which will be useful for treatment of immune related diseases. Since the sphingosine derivatives are very interesting both biologically and synthetically, recently many attempts have been tried to synthesize not only natural sphingosine derivatives but also new modifications of sphingosine derivatives for the evaluation of biological activities. Previously, we reported a novel synthesis of N-Bocphytosphingosine-3,4-carbonate as an intermediate for the synthesis of new phytosphingosine derivatives, however we could only modify 1-position of phytosphingosine from the intermediate. Here we wish to report a new synton for the synthesis of various sphingosine derivatives. N-Boc-Phytosphingosine (2) was reacted with phenyl chlorothionocarbonate and pyridine at 0 C in THF to afford 3 in good yield. To the reaction mixture was added 1.2 equiv of DBU at 25 C, the thiocarbonate at 1-position was migrated to 3position, and then the cyclic thiocarbonate 4 was formed as sticky solid in 65% yield as shown in Scheme 1. Hydrolysis of 4 with potassium carbonate in 95% methanol afforded N-Boc-phytosphingosine (2) quantitatively. For the reductive elimination of 4, first we examined tributyltin hydride or triphenyltin hydride in the presence of triethylborane, but the reaction did not occur at all. When 4 was heated in toluene with tri(trimethylsilyl)silane in the presence of cat. AIBN, the thiocarbonate group in 4 was reduced to the double bond to form 5 and 6 in a ratio of 2 : 1 in total 80% yields, while after protection of hydroxyl group of 4 with TBDMS, the trans double bond (8) was formed as a major in a ratio of 9 : 1 as shown in Scheme 2. The aminoalcohols, 5 and 6 showed potent biological

Synthesis and Biological Evaluation of 2′,3′-Didehydro-2′,3′-Dideoxy-9-Deazaguanosine, a Monophosphate Prodrug and Two Analogues, 2′,3′-Dideoxy-9-Deazaguanosine and 2′,3′-Didehydro-2′,3′-Dideoxy-9-Deazainosine

2′,3′-Didehydro-2′,3′-dideoxy-9-deazaguanosine (1), its monophosphate prodrug (2), and two analogues, 2′,3′-dideoxy-9-deazaguanosine (3) and 2′,3′-didehydro-2′,3′-dideoxy-9-deazainosine (4), have been synthesized from benzoylated 9-deazaguanosine (5). Basic hydrolysis of 5, selective protection of the 2-amino and 5′-hydroxy functions with isobutyryl and silyl groups, respectively, followed by reaction with thiocarbonyldiimidazole gave the cyclic thiocarbonate, which, upon reaction with triethyl phosphite, followed by deprotection, afforded 1. Treatment of 1 with phenyl methoxyalaninyl phosphochloridate and N-methylimidazole gave 2. Catalytic hydrogenation of 1 gave 3. Hydrodediazoniation of 1 with tert-butyl nitrite and tris(trimethylsilyl)silane gave 4. Compounds 1–4 were found to be inactive against the human immunodeficiency virus and exhibited minimal to no cytotoxic activity against the L1210 leukemia, CCRF-CEM lymphoblastic leukemia, and B16F10 melanoma in vitro. This research was supported in part by a Drug Discovery and Development Award from GlaxoSmithKline.

Enantioselective Total Synthesis of 3‐epi‐Ottelione A.

An enantioselective total synthesis of (+)-3-epi-ottelione A (2), the earlier proposed stereostructure of the antitumor natural product ottelione A (4), was achieved for the first time starting from the known tetracyclic compound 9. The synthesis involves the following three crucial steps: (i) a coupling reaction of aldehyde 8 and aryllithium 7 to introduce the aromatic portion, (ii) base-induced lactol-opening/epimerization at the C1 position of 6 to deliver the requisite hydrindane 15, and (iii) Corey-Winter's reductive olefination of the cyclic thiocarbonate 19 to install the C5-C6 double bond.

Living ring‐opening polymerization of cyclic thiocarbonate

AbstractThis work deals with the cationic ring‐opening polymerization of a cyclic thiocarbonate, 5,5‐dimethyl‐1,3‐dioxane‐2‐thione (1). The polymerization was carried out with 2 mol% of trifluoromethanesulfonic acid, methyl trifluoromethanesulfonate, boron trifluoride etherate, or triethyloxonium tetrafluoroborate as an initiator to afford the polythiocarbonate with the narrow molecular weight distribution (Mn = 11200‐31000, Mw/Mn = 1.04‐1.15). The molecular weight of the obtained polymer could be controlled by the feed ratio of the monomer to the initiator and increased when the second monomer was added to the polymerization mixture after quantitative consumption of 1 in the first stage, supporting that the cationic ring‐opening polymerization of 1 proceeded via a living process.

Cationic ring‐opening polymerization behavior of a five‐membered cyclic thiocarbonate having a spiro‐linked adamantane moiety

AbstractThis work deals with the synthesis and cationic ring‐opening polymerization behavior of a novel five‐membered cyclic thiocarbonate bearing a spiro‐linked adamantane moiety, tricyclo[3.3.1.13,7]decane‐2‐spiro‐4′‐(1′,3′‐dioxolane‐2′‐thione) (TC2). The cationic ring‐opening polymerization of TC2 did not proceed with trifluoromethanesulfonic acid, methyl trifluoromethanesulfonate, triethyloxonium tetrafluoroborate (Et3OBF4), boron trifluoride etherate (BF3OEt2), titanium tetrachloride, or methyl iodide as the initiator, presumably because of the steric hindrance of the adamantane moiety. However, the cationic ring‐opening copolymerization of TC2 with five‐ or six‐membered cyclic thiocarbonates, that is, 1,3‐dioxolane‐2‐thione, 1,3‐dioxane‐2‐thione, 5‐methyl‐1,3‐dioxane‐2‐thione, or 5,5‐dimethyl‐1,3‐dioxane‐2‐thione, initiated by BF3OEt2 or Et3OBF4, proceeded to afford the corresponding copolymer via a selective ring‐opening direction. The increase in the feed ratio of TC2 in the copolymerization increased the unit ratio derived from TC2 in the copolymer; however, the molecular weight of the copolymer decreased. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 699–707, 2003

Enantioselective Total Synthesis of 3-epi-Ottelione A

An enantioselective total synthesis of (+)-3-epi-ottelione A (2), the earlier proposed stereostructure of the antitumor natural product ottelione A (4), was achieved for the first time starting from the known tetracyclic compound 9. The synthesis involves the following three crucial steps: (i) a coupling reaction of aldehyde 8 and aryllithium 7 to introduce the aromatic portion, (ii) base-induced lactol-opening/epimerization at the C1 position of 6 to deliver the requisite hydrindane 15, and (iii) Corey-Winter's reductive olefination of the cyclic thiocarbonate 19 to install the C5-C6 double bond.

Controlled cationic ring-opening polymerization of cyclic thiocarbonates with ester groups

This work deals with the cationic ring-opening polymerization of the cyclic thiocarbonates 5-benzoyloxymethyl-5-methyl-1,3-dioxane-2-thione (1), 5,5-dimethyl-1,3-dioxane-2-thione (2), and 4-benzoyloxymethyl-1,3-dioxane-2-thione (3). The polymerization was carried out with 2 mol % trifluoromethanesulfonic acid, methyl trifluoromethanesulfonate, boron trifluoride etherate, or triethyloxonium tetrafluoroborate as the initiator to afford the polythiocarbonate with a narrow molecular weight distribution accompanying isomerization of the thiocarbonate group. The molecular weight of the obtained polymer could be controlled by the feed ratio of the monomer to the initiator and increased when the second monomer was added to the polymerization mixture after the quantitative consumption of the monomer in the first stage. The block copolymerization of 2 and 3 was also achieved, and this supported the idea that the cationic ring-opening polymerization of these monomers proceeded via a living process. The order of the polymerization rate was 3 > 2 > 1. The cationic ring-opening polymerization of 1 and 3 involved the neighboring group participation of ester groups according to the polymerization rate and molecular orbital calculations with the ab initio method. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 185–195, 2003

Cationic Ring-Opening Polymerization of Five-Membered Cyclic Thiocarbonate Bearing an Adamantane Moiety via Selective Ring-Opening Direction

A novel five-membered cyclic thiocarbonate bearing adamantane moiety, 4,6-dioxatetracyclo[6.3.1.1.3,1003,7]tridecane-5-thione (1), was synthesized from 1,2-adamantanediol and thiophosgene in the presence of pyridine. Monomer 1 underwent cationic ring-opening polymerization initiated by triethyloxonium tetrafluoroborate (Et3OBF4), methyl trifluoromethanesulfonate (TfOMe), trifluoromethanesulfonic acid (TfOH), and H2O with 2 mol % of boron trifluoride etherate (BF3OEt2) in CH2Cl2 at 30 °C to afford the polythiocarbonate by isomerization of the thiocarbonyl group into a carbonyl group with selective ring-opening direction. The number-average molecular weight and polydispersity of the polymer obtained by polymerization with H2O/BF3OEt2 were 10 600 and 1.44, respectively. The temperature with 5% weight loss of the obtained polymer was 338 °C. Monomer 1 expanded as large as 14% during the polymerization.

Cationic ring-opening polymerization of monothiocarbonate with a norbornene group

This work deals with the cationic ring-opening polymerization of cyclic thiocarbonates with a norbornene or norbornane moiety, that is, 5,5-(bicyclo[2.2.1]hept-2-ene-5,5-ylidene)-1,3-dioxane-2-thione (TC1) or 5,5-(bicyclo[2.2.1]heptane-5,5-ylidene)-1,3-dioxane-2-thione (TC2), respectively. The reaction of TC1 initiated by trifluoromethanesulfonic acid (TfOH), methyl trifluoromethanesulfonate (TfOMe), boron trifluoride etherate (BF3OEt2), or triethyloxonium tetrafluoroborate (Et3OBF4) afforded unidentified products; however, TC1 underwent cationic ring-opening polymerization with methyl iodide as an initiator to afford polythiocarbonate because the propagating end was stabilized by the covalent-bonding property. The polymerization of TC2 initiated by TfOH, TfOMe, BF3OEt2, or Et3OBF4 afforded polythiocarbonate with good solubility in common organic solvents and a narrow molecular weight distribution because of the absence of a double-bond moiety. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1698–1705, 2002

Anionic Ring-Opening Polymerization of Cyclic Thiocarbonates Containing Norbornene and Norbornane Groups Undergoing Volume Expansion on Polymerization

Abstract Six-membered cyclic thiocarbonate derivatives, 5,5-(bicyclo[2.2.1]hept-2-en-5,5-ylidene)-1,3-dioxane-2-thione (1) and 5,5-(bicyclo[2.2.1]heptan-5,5-ylidene)-1,3-dioxane-2-thione (2) underwent anionic ring-opening polymerization initiated by 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) to afford polythiocarbonates accompanying 12.3 and 12.6% volume expansion, respectively.

Polyaddition of Bis(cyclic thiocarbonate) with Diamines. Novel Efficient Synthetic Method of Polyhydroxythiourethanes

The polyaddition of a five-membered bis(cyclic thiocarbonate), 2,2-bis[p-(1,3-dioxolane-2-thione-4-yl-methoxy)phenyl]propane (B5CTC) with diamines, 4,9-dioxa-1,12-dodecanediamine (DODDA), and p-xylylenediamine (p-XDA) was carried out to afford the corresponding polyhydroxythiourethanes with number-average molecular weights of 11 000−44 000 in good yields. The rate of polyaddition of B5CTC was extremely larger than the corresponding five-membered bis(cyclic carbonate), 2,2-bis[p-(1,3-dioxolan-2-one-4-yl-methoxy)phenyl]propane (B5CC). Also, B5CTC gave higher molecular weight polymers than B5CC. These differences were discussed based on the reaction process of a monofunctional five-membered cyclic thiocarbonate and a cyclic carbonate with amines.

ChemInform Abstract: Synthesis of Furanose Glycals from Furanose 1,2‐Diols and Their Cyclic Thiocarbonate Esters.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of furanose glycals from furanose 1,2-diols and their cyclic thiocarbonate esters

Two new methods for the synthesis of furanoid glycals are described. Both procedures were shown to be faster and cheaper that those previously reported. Protected 1,2-dihydroxypento- and hexo-furanose derivatives with the d- xylo, d- gluco and d- ribo, d- allo configurations were used as starting material to afford the corresponding C-3,4 d- threo and d- erythro glycals derivatives.

Total Synthesis of (+)-Lactacystin from (R)-Glutamate

The discovery by dmura' of (+)-lactacystin (1) in Streptomycessp. OM-65 19 and the finding that it possesses neurotrophic activity have created much excitement, since the role of neurotrophic proteins, such as nerve growth factors (NGFs), in diseases is the center of much current interest.2 This substance consists of two a-amino acids, (R)-N-acetylcysteine and a novel pyroglutamic acid derivative 2. The combination of biological activity and the unique structure of lactacystin encouraged us to develop a synthesis which could permit variations of both the substituents and their stereochemistry. During the course of our work two elegant syntheses were r e p ~ r t e d , ~ . ~ which are strategically different from our route. The key reaction in our synthesis involves the stereoselective aldol reaction of a siloxypyrrole, readily available from pyroglutamate, with an aldehyde, thereby assembling the quaternary center and secondary alcohol in the correct stereochemical form, Scheme 1. The bicyclic oxazolidine 3 was prepared from (R)-glutamic acid in three steps (57%)5 and was elaborated to the unsaturated derivative 4 by sequential methylation6 and selenenylation/ozonolysis (65%, Scheme 2). The key siloxypyrrole 5 was obtained as a crystalline solid (89%) by treatment with TBSOTf and 2,6-lutidine.' The aldol reaction of 5 with isobutyraldehyde was achieved at -78 OC in ether in the presence of 2 equiv of SnC14 to afford 68 and its secondary alcohol epimers in the ratio 9: 1. The major isomer 6 was obtained as a crystalline solid after chromatography (55% yield). The surprising *-facial selectivity observed here, i.e., addition to the same face as the phenyl substituent, was revealed by X-ray crystallography of thep-bromobenzoate derivative of er1t-6.~ Use of other Lewis acids and solvents led to the formation of other isomers at the quaternary and secondary alcohol centers,1° thereby permitting access to these substances. Following acetylation 7 was converted to the diol 8 as a single isomer (87%) by osmylation (OsO,, N-methylmorpholine N-oxide). The tertiary hydroxyl group was removed via the cyclic thiocarbonate with Bu3SnH in

Novelp-Toluenesulfonylation and Thionocarbonylation of Unprotected Thymine Nucleosides

A new procedure involving the use of both dibutyltin oxide and a quaternary ammonium salt along with p-toluenesulfonyl chloride or phenoxythiocarbonyl chloride leads in good yields to the desired monotosylate or to the 2′,3′-O -cyclic thiocarbonate of thymine nucleosides without prior modification of any hydroxyl group. It is noteworthy that with 5-methyl uridine, tosylation occurs regioselectively at the 2′- position, while the 3′-O-tosylate is formed when 5-methyl uridine is substituted on 1′ by a methyl (or cyano) group.

ChemInform Abstract: The Synthesis and Reactivity of Cyclic Thiocarbonates Derived from Some Carbohydrate 1,2‐Diols.

AbstractThiocarbonylation of diols such as (I) leads to the corresponding cyclic thiocarbonates (III) and (IV).

ChemInform Abstract: Unusual Reaction of Cyclic Thiocarbonates, e.g. (I), with Secondary Amines (II).

ChemInformVolume 20, Issue 51 Heterocyclic Compounds ChemInform Abstract: Unusual Reaction of Cyclic Thiocarbonates, e.g. (I), with Secondary Amines (II). A. G. MAL'KINA, A. G. MAL'KINA Irkutsk. inst. org. khim. Sib. otd. AN SSSR, Irkutsk 664033Search for more papers by this authorYU. M. SKVORTSOV, YU. M. SKVORTSOV Irkutsk. inst. org. khim. Sib. otd. AN SSSR, Irkutsk 664033Search for more papers by this authorE. I. MOSHCHEVITINA, E. I. MOSHCHEVITINA Irkutsk. inst. org. khim. Sib. otd. AN SSSR, Irkutsk 664033Search for more papers by this authorV. K. BEL'SKII, V. K. BEL'SKII Irkutsk. inst. org. khim. Sib. otd. AN SSSR, Irkutsk 664033Search for more papers by this authorV. A. TROFIMOV, V. A. TROFIMOV Irkutsk. inst. org. khim. Sib. otd. AN SSSR, Irkutsk 664033Search for more papers by this author A. G. MAL'KINA, A. G. MAL'KINA Irkutsk. inst. org. khim. Sib. otd. AN SSSR, Irkutsk 664033Search for more papers by this authorYU. M. SKVORTSOV, YU. M. SKVORTSOV Irkutsk. inst. org. khim. Sib. otd. AN SSSR, Irkutsk 664033Search for more papers by this authorE. I. MOSHCHEVITINA, E. I. MOSHCHEVITINA Irkutsk. inst. org. khim. Sib. otd. AN SSSR, Irkutsk 664033Search for more papers by this authorV. K. BEL'SKII, V. K. BEL'SKII Irkutsk. inst. org. khim. Sib. otd. AN SSSR, Irkutsk 664033Search for more papers by this authorV. A. TROFIMOV, V. A. TROFIMOV Irkutsk. inst. org. khim. Sib. otd. AN SSSR, Irkutsk 664033Search for more papers by this author First published: December 19, 1989 https://doi.org/10.1002/chin.198951159Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume20, Issue51December 19, 1989 RelatedInformation

Unusual reaction of a cyclic thiocarbonate with secondary amines

Opening of the 1,3-oxathiolane ring with the formation of 8-mercaptoalkylcarbamate II evidently occurs in the first step under the influence of the amine; the subsequent dimerization of II via the addition of the mercapto group of one molecule to the double bond of a second molecule leads to intermediate III. This is followed by intramolecular substitution of the carbamoyl grouping with the formation of the 1,3-dithiolane ring.

The Synthesis and Reactivity of Cyclic Thiocarbonates Derived From Some Carbohydrate 1,2-Diols

The attempted synthesis of several carbohydrate 1,2-diols is reported, together with the transformation of two of these diols into cyclic thiocarbonates, namely 4,6-O-benzylidene-3-O-methyl-1,2-O-thiocarbonyl-a-D-glucose and 3,4-O-isopropylidene-1,2-O-thiocarbonyl-β-D-arabinose. The treatment of these thiocarbonates, and a furanose 1,2-thiocarbonate previously prepared by Mukaiyama, with methyl halides and with tributyltin hydride is discussed. A single-crystal X-ray diffraction study of 3,4-O-isopropylidene-1,2-O-thiocarbonyl-β-D-arabinose is recorded.