WO2010041964A1 - Procédés pour la préparation d'alcénylamines, de carbamates cycliques ou de dithiocarbamates, et d'aminoalcools ou d'aminothiols - Google Patents

Procédés pour la préparation d'alcénylamines, de carbamates cycliques ou de dithiocarbamates, et d'aminoalcools ou d'aminothiols Download PDF

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WO2010041964A1
WO2010041964A1 PCT/NZ2009/000216 NZ2009000216W WO2010041964A1 WO 2010041964 A1 WO2010041964 A1 WO 2010041964A1 NZ 2009000216 W NZ2009000216 W NZ 2009000216W WO 2010041964 A1 WO2010041964 A1 WO 2010041964A1
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substituted
group
cycloalkyl
heterocyclyl
independently selected
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PCT/NZ2009/000216
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English (en)
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Emma M. Dangerfield
Bridget L. Stocker
Mattheus S. M. Timmer
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Victoria Link Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/24—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds
    • C07C209/28—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds by reduction with other reducing agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
    • C07C215/24—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and acyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems

Definitions

  • the present invention relates to methods for preparing alkenylamines from cyclic acetals or derivatives thereof, methods for preparing cyclic carbamates and cyclic dithiocarbamates from alkenylamines, and methods for preparing aminoalcohols and aminothiols from cyclic carbamates and cyclic dithiocarbamates, respectively. More particularly, the present invention relates to regio- and stereo-selective methods for preparing these compounds.
  • polyhydroxylated alkaloids Owing to their properties as inhibitors of glycosidases, polyhydroxylated alkaloids have enormous therapeutic potential in diseases such as viral infection, bacterial infection, lysosomal storage disorders, cancer and diabetes.
  • the nature of the glycosidases that will be inhibited by certain imino-sugars may, to some extent, be predicted from the number, position and configuration of the substituents.
  • isoenzymes of a given glycosidase in different species and even within the same cell.
  • Many tumour cells display aberrant glycosylation due to an altered expression of glycosyltransferases and levels of glycosidases are elevated in the sera of many patients with tumours.
  • Five-membered imino-sugars also known as hydroxypyrrolidines, include: the ⁇ -galactosidase inhibitor l,4-dideoxy-l,4-imino-D-lyxitol (A); the mannosidase inhibitors l,4-dideoxy-l,4- imino-D-mannitol (B) and l,4,6-trideoxy-l,4-imino-D-mannitol (C); l,4-dideoxy-l,4-imino-D- xylitol (D); l,4-dideoxy-l,4-imino-L-lyxitol (E); swainsonine, which inhibits both lysosomal ⁇ - mannosidase and monosidase II; the potent inhibitor of ⁇ -galactosidase and ⁇ -mannosidase, broussonetinine A (F); guala
  • the present invention provides a method for preparing an alkenylamine, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide the alkenylamine; optionally converting the alkenylamine into a salt, solvate or hydrate thereof; and optionally isolating the alkenylamine or salt, solvate or hydrate thereof.
  • the present invention provides a method for preparing a cyclic carbamate or cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting an alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the cyclic carbamate or cyclic dithiocarbamate; optionally converting the cyclic carbamate or cyclic dithiocarbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or cyclic dithiocarbamate or salt, solvate or hydrate thereof.
  • the present invention provides a method for preparing a cyclic carbamate or cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the cyclic carbamate or cyclic dithiocarbamate; optionally converting the cyclic carbamate or cyclic dithiocarbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or cyclic dithiocarbamate or salt, solvate or hydrate thereof.
  • the present invention provides a method for preparing a 1,2-aminoalcohol or 1,2-aminothiol, or a salt, solvate or hydrate thereof, the method comprising: reacting an alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate; deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the 1,2-aminoalcohol or 1,2-aminothiol; optionally converting the 1,2-aminoalcohol or 1,2-aminothiol into a salt, solvate or hydrate thereof; and optionally isolating the 1 ,2-aminoalcohol or 1 ,2-aminothiol or salt, solvate or hydrate thereof.
  • the present invention provides a method for preparing a 1,2-aminoalcohol or
  • 1,2-aminothiol, or a salt, solvate or hydrate thereof the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate; deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the 1,2-aminoalcohol or
  • 1,2-aminothiol optionally converting the 1,2-aminoalcohol or 1,2-aminothiol into a salt, solvate or hydrate thereof; and optionally isolating the 1,2-aminoalcohol or 1,2-aminothiol or salt, solvate or hydrate thereof.
  • the invention also provides an alkenylamine, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.
  • the invention also provides a cyclic carbamate, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.
  • the invention also provides a cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.
  • the invention also provides a 1,2-aminoalcohol, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.
  • the invention also provides a 1,2-aminothiol, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.
  • the invention also provides the halogen-substituted cyclic acetal:
  • the invention also provides an alkenylamine selected from the group consisting of:
  • the invention also provides a cyclic carbamate selected from the group consisting of:
  • This invention may also be said broadly to consist in the parts, elements and features referred to or indicated in the specification of the application, individually or collectively, and any or all combinations of any two or more said parts, elements or features, and where specific integers are mentioned herein which have known equivalents in the art to which this invention relates, such known equivalents are deemed to be incorporated herein as if individually set forth.
  • salt is intended to include acid addition salts of any basic moiety that may be present in a compound useful in the invention, and base addition salts of any acidic moiety that may be present in a compound useful in the invention.
  • Such salts are generally prepared by reacting the compound with a suitable organic or inorganic acid or base.
  • Examples of salts of basic moieties include: sulfates; methanesulfonates; acetates; hydrochlorides; hydrobromides; phosphates; toluenesulfonates; citrates; maleates; succinates; tartrates; lactates; and fumarates.
  • salts of acidic moieties include: ammonium salts; alkali metal salts such as sodium salts and potassium salts; and alkaline earth metal salts such as calcium salts and magnesium salts. Other salts will be apparent to those skilled in the art.
  • the compounds useful in the invention, and their salts or other derivatives, may form hydrates, or solvates with various solvents.
  • the present invention contemplates such hydrates and solvates as well as the corresponding unsolvated forms.
  • the compounds useful in the invention may have asymmetric carbon atoms. Therefore, stereoisomers (both enantiomers and diastereomers) of such compounds can exist.
  • the present invention contemplates the pure stereoisomers and any mixture of the isomers.
  • a pure enantiomer of a compound can be isolated from a mixture of enantiomers of the compound using conventional optical resolution techniques. Enol forms and tautomers are also contemplated, where appropriate.
  • the invention also contemplates "radiolabeled compounds", which are compounds that contain unnatural proportions of atomic isotopes. Such compounds may be useful as therapeutic, diagnostic or research reagents.
  • alkyl is intended to include straight chain and branched chain saturated hydrocarbon groups.
  • alkyl groups comprise 1 to 30 carbon atoms.
  • alkyl groups comprise the aliphatic chain of a short chain, medium chain or long chain fatty acid.
  • alkyl groups comprise 1 to 6 carbon atoms.
  • the alkyl group is methyl, ethyl, n-propyl, i-propyl, n-butyl, i- butyl or t-butyl;
  • cycloalkyr' is intended to include cyclic saturated hydrocarbon groups
  • alkenyl is intended to include straight chain and branched chain unsaturated hydrocarbon groups;
  • cycloalkenyl is intended to include cyclic unsaturated hydrocarbon groups;
  • alkynyl is intended to include straight chain and branched chain hydrocarbon groups including a carbon-carbon triple bond
  • alkoxy is intended to include alkyl-O- groups
  • cycloalkoxy is intended to include cycloalkyl-O- groups
  • aryl is intended to include aromatic radicals including, but not limited to: phenyl; naphthyl; indanyl; biphenyl; and the like.
  • preferred aryl groups comprise 4 to 10 ring carbon atoms;
  • amino is intended to include -NH 2 groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group;
  • amino is intended to include amino-C(O)- groups
  • aryloxy is intended to include aryl-O- groups
  • heteroaryl is intended to include heteroaromatic radicals including, but not limited to: pyrimidinyl; pyridyl; pyrrolyl; furyl; oxazolyl; thiophenyl; and the like;
  • heteroaryloxy is intended to include heteroaryl-O- groups
  • heterocyclyl is intended to include non-aromatic heterocyclic radicals including, but not limited to: piperidinyl; pyrrolidinyl; piperazinyl; 1,4-dioxanyl; tetrahydrofuranyl; tetrahydrothiophenyl; and the like;
  • heterocyclyloxy is intended to include heterocyclyl-O- groups
  • acyl is intended to include -C(O)R groups, wherein R is an optionally substituted alkyl or aryl group;
  • carboxyl is intended to include -C(O)OH groups, wherein the hydrogen atom may be replaced by an optionally substituted alkyl or aryl group or a cation;
  • halo is intended to mean chloro, bromo, fluoro, or iodo;
  • metal is intended to include, but is not limited to: lithium; sodium; potassium; magnesium; calcium; aluminium; manganese; nickel; copper; zinc; and tin;
  • oxy is intended to mean the -O- group
  • borane is intended to include -BH 2 groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group;
  • boronic is intended to include -B(OH) 2 groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group or a metal;
  • phosphate is intended to include -OP(O)(OH) 2 groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group or a metal;
  • phosphinate is intended to include -OP(O)H 2 and -P(O)(OH)H groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group or a metal;
  • phosphine is intended to include -PH 2 groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group;
  • phosphite is intended to include -OP(OH) 2 groups wherein one or both of the - hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group or a metal;
  • phosphonate is intended to include -P(O)(OH) 2 and -OP(O)(OH)H groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group or a metal;
  • silane is intended to include -SiH 3 groups, wherein one, two or all three of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group;
  • siloxane is intended to include -Si(O)H groups, where the hydrogen atom may be replaced by an optionally substituted alkyl or aryl group or a metal
  • sulfate is intended to include -OS(O) 3 H groups, wherein the hydrogen atom may be replaced by an optionally substituted alkyl or aryl group or a metal
  • sulfenyl is intended to include -SR groups, wherein R is an optionally substituted alkyl or aryl group;
  • sulfonyl is intended to include -S(O) 2 R groups, wherein R is an optionally substituted alkyl or aryl group;
  • sulfoxide is intended to include -S(O)R groups, wherein R is an optionally substituted alkyl or aryl group.
  • substituted is intended to mean that one or more hydrogen atoms in the group indicated is replaced with one or more independently selected suitable substituents, provided that the normal valency of each atom to which the substituent/s are attached is not exceeded, and that the substitution results in a stable compound.
  • the substituents are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkyloxy, alkenyl, cycloalkenyl, alkoxy, aryl, aryloxy, heterocyclyl, heterocyclyloxy, heteroaryl, heteroaryloxy, acyl, carboxyl, amino, amido, imino, -NO 2 , -NO, -CN, -N 3 , -OH, sulfenyl, sulfonyl, sulfoxide, sulfate, phosphate, phosphonate, phosphinate, phosphine, phosphite and halo.
  • substituted sulfur is intended to include sulfate, sulfenyl, sulfonyl and sulfoxide groups.
  • substituted silicon is intended to include silane and siloxane groups.
  • substituted boron is intended to include borane and boronic groups.
  • substituted phosphorus is intended to include phosphate, phosphinate, phosphine, phosphite and phosphonate groups.
  • the present invention relates to a two-stage synthesis of 1,2-aminoalcohols or 1,2-aminothiols, in which a key step is the formation of a cyclic carbamate or cyclic dithiocarbamate from a precursor alkenylamine.
  • the alkenylamines are accessible in one step from halogenated cyclic acetals or derivatives thereof.
  • the methods of the present invention provide facile access to compounds for use in myriad applications, whether as synthetic intermediates, pharmaceutical compounds or chiral ligands for asymmetric synthesis.
  • Scheme I illustrates the preparation of an alkenylamine of Formula I from a halogen-substituted cyclic acetal or a derivative thereof of Formula II.
  • Y is O.
  • Preferred halogen-substituted cyclic acetals include an alkoxy, substituted alkoxy, alkenyloxy or aryloxy leaving group, more preferably an alkoxy leaving group.
  • Preferred halogen-substituted cyclic acetals and derivatives thereof include a leaving group selected from the group consisting of halogen, -OR 10 , -NHR 10 , -N(R 10 ) 2 , -SR 10 , -SOR 10 , -SO 2 R 10 and -SeR 10 , wherein R 10 is independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxy, substituted alkoxy, acyl, substituted acyl, acetimidoyl, substituted acetimidoyl, amino, substituted amino and halogen.
  • R 10 is independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl,
  • the present invention provides a method for preparing an alkenylamine, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide the alkenylamine; optionally converting the alkenylamine into a salt, solvate or hydrate thereof; and optionally isolating the alkenylamine or salt, solvate or hydrate thereof.
  • the halogen-substituted cyclic acetal or derivative thereof is enantiopure and the reaction is stereo- and regioselective, such that the resulting alkenylamine is chiral.
  • the halogen-substituted cyclic acetal or derivative thereof is stereoisomerically pure and the reaction is stereo- and regioselective, such that the resulting alkenylamine is stereoisomerically pure.
  • L is selected from the group consisting of:
  • R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 , R 42 , R 51 and R 52 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and
  • the compound of Formula II is selected from the group consisting of the compounds of Formula Ha, lib and Hc:
  • the compound of Formula II is selected from the group consisting of the compounds of Formula Ha and lib.
  • the compound of Formula I is selected from the group consisting of the compounds of Formula Ia 5 Ib and Ic:
  • the compound of Formula I is selected from the group consisting of the compounds of Formula Ia and Ib.
  • the compound of Formula I has the Formula Ia:
  • R 11 , R 12 , R 21 and R 22 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I;
  • R and R and/or R and R together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R 11 and R 21 and/or R 12 and R 22 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • the compound of Formula I has the Formula Ia; wherein R 11 and R" are -H, and R 12 and R are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 12 and R 22 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • the compound of Formula I has the Formula Ia; wherein R 11 and R 21 are -H, and R 12 and R 22 are each independently selected from the group consisting of -H, -N 3 , -OR 2 and -NR 3 R , wherein R 2 , R 3 and R 4 at each occurrence are each independently selected from -H, -R 8 , -C(X)R 8 and -C(X)XR 8 ; X at each occurrence is independently selected from O, NH, NR and S; and
  • R 8 and R 9 at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.
  • the compound of Formula I has the Formula Ia; wherein R 11 and R 21 are -H, R 12 is -OH; and R 22 is selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • the compound of Formula I has the Formula Ia; wherein R ⁇ and R 21 are -H, and R 12 and R 22 are -OH.
  • the compound of Formula I has the Formula Ia; wherein R , R 21 and R 22 are -H, and R 12 is -OH.
  • the compound of Formula I has the Formula Ib:
  • R 11 , R 12 , R 21 , R 22 , R 31 and R 32 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 11 and R 12 , R 21 and R 22 , and/or R 31 and R 32 , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R 11 and R 21 , R 12 and R 22 , R 21 and R 31 , and/or R 22 and R 32 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted
  • the compound of Formula I has the Formula Ib; wherein R , R and R are -H, and R , R and R are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R and R and/or R and R together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • the compound of Formula I has the Formula Ib; wherein R 11 , R 21 and R 31 are -H, and R 12 , R 22 and R 32 are each independently selected from the group consisting of -H, -N 3 , -OR 2 and -NR 3 R , wherein R 2 , R 3 and R at each occurrence are each independently selected from -H, -R 8 , -C(X)R 8 and -C(X)XR 8 ; X at each occurrence is independently selected from O, NH, NR 9 and S; and
  • R and R at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.
  • the compound of Formula I has the Formula Ib; wherein R 11 , R 21 and R 31 are -H; R 12 is -OH; and
  • R 22 and R 32 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • the compound of Formula I has the Formula Ib; wherein R 11 , R 21 and R 31 are -H; R 12 and R 22 are -OH; and
  • R 32 is selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • the compound of Formula I has the Formula Ib; wherein R 11 , R 21 and R 31 are -H, and R 12 , R 22 and R 32 are -OH.
  • the compound of Formula I has the Formula Ib; wherein R l , R 21 , R 31 and R 32 are -H, and R 12 and R 22 are -OH.
  • the compound of Formula I has the Formula Ic:
  • R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 and R 42 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , and/or R 41 and R 42 , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cyeloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R 11 and R 21 , R 12 and R 22 , R 21 and R 31 , R 22 and R 32 , R 31 and R 41 , and/or R 32 and R 42 , together with the carbon atoms to which they are attached, form a
  • the compound of Formula I has the Formula Ic; wherein R 11 , R 21 , R 31 and R 41 are -H, and R 12 , R 22 , R 32 and R 42 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 12 and R 22 , R 22 and R 32 , and/or R 32 and R 42 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • the compound of Formula I has the Formula Ic; wherein R 11 , R 21 , R 31 and R 41 are -H, and R 12 , R 22 , R 32 and R 42 are each independently selected from the group consisting of -H, -N 3 , -OR 2 and -NR 3 R 4 , wherein R 2 , R 3 and R 4 at each occurrence are each independently selected from -H, -R 8 , -C(X)R 8 and -C(X)XR 8 ; X at each occurrence is independently selected from O, NH, NR 9 and S; and R 8 and R 9 at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, substituted hetero
  • the compound of Formula I has the Formula Ic; wherein R 11 , R 21 , R 31 and R 41 are -H; R 12 is -OH; and
  • R 22 , R 32 and R 42 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for
  • the compound of Formula I has the Formula Ic; wherein R 11 , R 21 , R 31 and R 41 are -H; R 12 and R 22 are -OH; and
  • R 32 and R 42 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • the compound of Formula I has the Formula Ic; wherein R 11 , R 21 , R 31 and R 41 are -H; and R 12 , R 22 , R 32 and R 42 are -OH.
  • the leaving group A is selected from the group consisting of halogen, -OR 10 , -NHR 10 , -N(R 10 ) 2 , -SR 10 , -SOR 10 , -SO 2 R 10 and -SeR 10 , wherein R 10 is independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxy, substituted alkoxy, acyl, substituted acyl, acetimidoyl, substituted acetimidoyl, amino, substituted amino and halogen.
  • R 10 is independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalky
  • the leaving group A is -OR 10 .
  • R 10 is alkyl
  • R 10 is alkyl, substituted alkyl, alkenyl or aryl.
  • R 10 is selected from the group consisting of methyl, ethyl, propyl, butyl, allyl, phenyl and benzyl.
  • R 10 is methyl
  • Z is selected from the group consisting of -I, -Br and -Cl.
  • Z is -I.
  • the reaction metal is selected from the group consisting of lithium, sodium, potassium, zinc, barium, magnesium, titanium, zirconium, indium, and mixtures of any two or more thereof.
  • the reaction metal is an alloy.
  • Preferred alloys include amalgams, such as Zn(Hg) and Na(Hg).
  • the reaction metal is zinc.
  • the source of ammonia is NH 3 .
  • the NH 3 may be ammonia gas, a solution of ammonia or a mixture thereof.
  • the solution may be aqueous ammonia or a solution of ammonia in an organic solvent, for example an alcoholic ammonia solution.
  • Preferred alcoholic ammonia solutions comprise a solution of ammonia in methanol or ethanol.
  • the source of ammonia is an ammonium salt.
  • the ammonium salt is selected from the group consisting OfNH 4 OH, NH 4 Cl, NH 4 OAc, NH 4 HCO 2 , NH 4 HSO 4 , (NH 4 ) 2 SO 4 , NH 4 HCO 3 , (NH 4 ) 2 CO 3 , and mixtures of any two or more thereof. More preferably, the ammonium salt is NH 4 OAc.
  • the source of ammonia is a mixture of NH 3 (for example, gaseous NH 3 and/or a solution ofNH 3 ) and one or more ammonium salt.
  • the hydride source must be sufficiently reactive to achieve the conversion of the halogen-substituted cyclic acetal or derivative thereof to the desired alkenylamine by reducing the intermediate iminium ion, without being so reactive that the intermediate aldehyde moiety is also reduced.
  • the hydride source is a metal hydride, such as lithium aluminium hydride or diisobutylaluminium hydride.
  • the hydride source is a borohydride.
  • Suitable borohydrides include, but are not limited to: NaBH 4 , NaBH 3 CN, LiBH 3 CN, NaBH 3 CN-ZnCl 2 , NaBH 3 CN-Ti(OzPr) 4 , NaBH 3 CN-Mg(C10 4 ) 2 , ( ⁇ -Bu) 4 NBH 3 CN, NaBH(OAc) 3 , NaBH 4 -NiCl 2 , NaBH 4 -ZnCl 2 , NaBH 4 - ZrCl 4 , Ti(OrPr) 4 -NaBH 4 , and NaBH 4 -H 2 SO 4 .
  • Resins (borohydride exchange resin) and clays (NaBH 4 on wet clay) may also be suitable.
  • the borohydride is sodium cyanoborohydride (NaBH 3 CN) or sodium triacetoxyborohydride (NaBH(O Ac) 3 ) .
  • NaBH 3 CN is stable in relatively strong acid solutions (pH 3), and is soluble in hydroxy lie solvents such as methanol. It also has different selectivities at different pH values. At pH 3-4 it reduces aldehydes and ketones effectively, but this reduction becomes very slow at higher pH values. At pH 6-8, the more basic imines are protonated preferentially and reduced faster than aldehydes or ketones.
  • Alternative hydride sources include the use of Lewis-acid catalysis, with reagents such as NaBH 3 CN-ZnCl 2 , NaBH 3 CN-Ti(OzPr) 4 , NaBH 4 -ZnCl 2 , NaBH 4 -ZrCl 4 , and Ti(OzPr) 4 -NaBH 4 .
  • Some of these milder Lewis acids, for example ZnCl 2 may stabilise the hydride reducing agent in aqueous media.
  • a further alternative hydride source is sodium borohydride activated by boric acid.
  • hydride sources include: nickel boride; Zn(BH 4 ) 2 , Zn(BH 4 ) 2 -ZnCl 2 , Zn(BH 4 ) 2 - SiO 2 , Zn-AcOH, polymethylhydrosiloxane (PMHS)-Ti(OzPr) 4 , PMHS-ZnCl 2 , PMHS- BuSn(OCOR) 3 , Et 3 SiH-CF 3 CO 2 H, (PhMe 2 )SiH-(C 6 Fe) 3 , Cl 3 SiH-DMF, PhSiH 3 -Bu 2 SnCl 2 , n- Bu 3 SnH-DMF or HMPA, H-Bu 3 SnH-SiO 2 and ⁇ -Bu 2 SnIH or W-Bu 2 SnClH.
  • nickel boride Zn(BH 4 ) 2 , Zn(BH 4 ) 2 -ZnCl 2 , Zn(BH 4 ) 2
  • Borane reducing agents including, but not limited to: pyridine-borane; picoline-borane; diborane-MeOH; and decaborane; are other alternative hydride sources.
  • the compounds of Formula II may be prepared by, for example: halogen substitution of an alkyl hydroxymethylfuranoside using triphenylphosphine and iodine (Skaanderup, P. R.; Poulsen, C. S.; Hyldtoft, L.; J ⁇ rgensen, M. R.; Madsen, R. Synthesis 2002, 12, 1721-1727); halogen substitution of an alkyl (methanesulfonyloxymethyl)furanoside with tetrabutylammonium iodide in benzene (Paquette, L.A.; Pissarnitski, D; Barriault, L. J Org Chem.
  • the invention also provides a compound of Formula I 5 or a salt, solvate or hydrate thereof, when prepared by a method of the invention.
  • the compound of Formula II is enantiopure and the resulting compound of Formula I is chiral.
  • the compound of Formula II may be resolved into enantiomers using methods known to those persons skilled in the art.
  • the compound of Formula II is stereoisomerically pure and the resulting compound of Formula I is stereoisomerically pure.
  • the present invention provides method for preparing a cyclic carbamate or cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting an alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the cyclic carbamate or cyclic dithiocarbamate; optionally converting the cyclic carbamate or cyclic dithiocarbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or cyclic dithiocarbamate or salt, solvate or hydrate thereof.
  • the method of the invention permits the efficient preparation of a cyclic carbamate or cyclic dithiocarbamate from an alkenylamine, since it provides concomitant installation of nitrogen protection.
  • the method does not require a 1,2-aminoalcohol or 1,2-aminothiol starting material, it provides a useful means to stereoselectively prepare these important functional motifs from an alkenylamine using simple reagents.
  • the alkenylamine is enantiopure and the reaction is stereo- and regioselective, such that the resulting cyclic carbamate or cyclic dithiocarbamate is chiral.
  • the alkenylamine is stereoisomerically pure and the reaction is stereo- and regioselective, such that the resulting cyclic carbamate or cyclic dithiocarbamate is stereoisomerically pure.
  • L is selected from the group consisting of:
  • R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 , R 42 , R 51 and R 52 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , R 41 and R 42 , and/or R 51 and R 52 , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R 11 and R 21 , R 12 and R 22 , R 21 and R 31 , R 22 and R 32 , R 31 and R 41 , R 32 and R 42 , R 41 and R 51
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 at each occurrence are independently selected from -H, -CN, -R 8 , -C(X)R 8 , -C(X)XR 8 , -C(R 8 ) 3 , -C(R 8 ) 2 XR 8 , -CR 8 (XR 8 ) 2 and -C(XR 8 ) 3 ; wherein X at each occurrence is independently selected from O, NH, NR 9 and S; and
  • Y is O.
  • the compound of Formula III is selected from the group consisting of the compounds of Formula Ilia, IHb and HIc:
  • the compound of Formula III is selected from the group consisting of the compounds of Formula HIa and HIb.
  • the compound of Formula III is selected from the group consisting of the compounds of Formula Ilia', IHb' and HIc':
  • the compound of Formula III is selected from the group consisting of the compounds of Formula Ilia' and IHb'.
  • the compound of Formula III has the Formula Ilia:
  • Y is O or S
  • R , R , R and R are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for
  • R 11 and R 12 and/or R 21 and R 22 together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R 11 and R 21 and/or R 12 and R 22 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • Y is O.
  • the compound of Formula III has the Formula Ilia; wherein Y is O or S;
  • R 11 and R 21 are -H
  • R 12 and R 22 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 12 and R 22 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl. More preferably, Y is O.
  • the compound of Formula III has the Formula Ilia; wherein Y is O or S;
  • R and R are -H, and R and R are each independently selected from the group consisting of -H, -N 3 , -OR 2 and -NR 3 R 4 , wherein R 2 , R 3 and R 4 at each occurrence are each independently selected from -H, -R 8 , -C(X)R 8 and -C(X)XR 8 ;
  • X at each occurrence is independently selected from O, NH, NR 9 and S; and R and R at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.
  • Y is O.
  • the compound of Formula III has the Formula Ilia; wherein Y is O or S;
  • R 11 and R 21 are -H
  • R 12 is -OH
  • R 22 is selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein
  • R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • Y is O.
  • the compound of Formula III has the Formula Ilia; wherein Y is O or S;
  • R 11 and R 21 are -H
  • R 12 and R 22 are -OH.
  • Y is O.
  • the compound of Formula III has the Formula Ilia; wherein Y is O or S;
  • R 11 , R 2! and R 22 are -H;
  • R 12 is -OH. More preferably, Y is O.
  • the compound of Formula III has the Formula Mb:
  • R 11 , R 12 , R 21 , R 22 , R 31 and R 32 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 11 and R 12 , R 21 and R 22 , and/or R 31 and R 32 , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R 11 and R 21 , R 12 and R 22 , R 21 and R 31 , and/or R 22 and R 32 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, substituted cycloal
  • Y is O.
  • the compound of Formula III has the Formula IHb; wherein Y is O or S;
  • R 11 , R 21 and R 31 are -H
  • R 12 , R 22 and R 32 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R and R and/or R" and R together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • Y is O.
  • the compound of Formula III has the Formula IHb; wherein Y is O or S; R 11 , R 21 and R 31 are -H, and R 12 , R 22 and R 32 are each independently selected from the group consisting of -H, -N 3 , -OR 2 and -NR 3 R 4 , wherein R 2 , R 3 and R 4 at each occurrence are each independently selected from -H, -R 8 , -C(X)R 8 and -C(X)XR 8 ; X at each occurrence is independently selected from O, NH, NR 9 and S; and R and R at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, ald heteroaryl
  • Y is O.
  • the compound of Formula III has the Formula IHb; wherein Y is O or S;
  • R 11 , R 21 and R 31 are -H;
  • R 12 is -OH
  • R 22 and R 32 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for
  • Y is O.
  • the compound of Formula III has the Formula IHb; wherein Y is O or S; R 11 , R 21 and R 31 are -H; R 12 and R 22 are -OH; and
  • R 32 is selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • Y is O.
  • the compound of Formula III has the Formula HIb; wherein Y is O or S;
  • R 11 , R 21 and R 31 are -H; and R 12 , R 22 and R 32 are -OH.
  • Y is O.
  • the compound of Formula III has the Formula IHb; wherein Y is O or S;
  • R 11 , R 21 , R 31 and R 32 are -H;
  • R 12 and R 22 are -OH.
  • Y is O.
  • the compound of Formula III has the Formula IHc:
  • Y is O or S
  • R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 and R 42 are each independently selected from the group consisting of -H 5 -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , and/or R 41 and R 42 , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R 11 and R 21 , R 12 and R 22 , R 21 and R 31 , R 22 and R 32 , R 31 and R 41 , and/or R 32 and R 42 , together with the carbon atoms to which they are attached, form a cyclic group
  • Y is O.
  • the compound of Formula III has the Formula IIIc; wherein Y is O or S;
  • R 11 , R 2i , R 31 and R 41 are -H
  • R 12 , R 22 , R 32 and R 42 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 12 and R 22 , R 22 and R 32 , and/or R 32 and R 42 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, siibstituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • Y is O.
  • the compound of Formula III has the Formula IHc; wherein Y is O or S;
  • R 11 , R 21 , R 31 and R 41 are -H
  • R 12 , R 22 , R 32 and R 42 are each independently selected from the group consisting of -H, -N 3 , -OR 2 and -NR 3 R 4 , wherein R 2 , R 3 and R 4 at each occurrence are each independently selected from -H, -R 8 , -C(X)R 8 and -C(X)XR 8 ; X at each occurrence is independently selected from O, NH, NR 9 and S; and R 8 and R 9 at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted
  • Y is O.
  • the compound of Formula III has the Formula IHc; wherein Y is O or S;
  • R 11 , R 21 , R 31 and R 41 are -H;
  • R 12 is -OH; and R 5 R and R are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • Y is O.
  • the compound of Formula III has the Formula IHc; wherein Y is O or S;
  • R 11 , R 21 , R 31 and R 41 are -H;
  • R 12 and R 22 are -OH;
  • R 32 and R 42 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I. More preferably, Y is O.
  • the compound of Formula III has the Formula IHc; wherein Y is O or S;
  • R 11 , R 21 , R 31 and R 41 are -H; and R 12 , R 22 , R 32 and R 42 are -OH.
  • Y is O.
  • the compound of Formula I is obtained by reacting a compound of Formula II as in the first aspect.
  • the halogen source is selected from the group consisting of NIS, NBS, NCS, I 2 , Br 2 , Cl 2 , and mixtures of any two or more thereof.
  • the halogen source is I 2 .
  • the source of carbonate is selected from the group consisting OfLiHCO 3 , Li 2 CO 3 , NaHCO 3 , Na 2 CO 3 , KHCO 3 , K 2 CO 3 , and mixtures of any two or more thereof.
  • the source of carbonate is NaHCO 3 .
  • the source of carbon dioxide is selected from the group consisting of carbon dioxide gas, liquid carbon dioxide, solid carbon dioxide, and mixtures of any two or more thereof.
  • the source of carbon disulfide is CS 2 .
  • the invention also provides a compound of Formula III, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.
  • the compound of Formula I is enantiopure and the resulting compound of Formula III is chiral. If necessary, the compound of Formula I may be resolved into enantiomers using methods known to those persons skilled in the art.
  • the compound of Formula I is stereoisomerically pure and the resulting compound of Formula III is stereoisomerically pure.
  • the present invention provides a method for preparing a cyclic carbamate or cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the cyclic carbamate or cyclic dithiocarbamate; optionally converting the cyclic carbamate or cyclic dithiocarbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or cyclic dithiocarbamate or salt, solvate or hydrate thereof.
  • the halogen-substituted cyclic acetal or derivative thereof is enantiopure and the reactions are stereo- and regioselective, such that the resulting cyclic carbamate or cyclic dithiocarbamate is chiral.
  • the halogen-substituted cyclic acetal or derivative thereof is stereoisomerically pure and the reactions are stereo- and regioselective, such that the resulting cyclic carbamate or cyclic dithiocarbamate is stereoisomerically pure.
  • a preferred embodiment of the third aspect provides a method for preparing a cyclic carbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide to provide the cyclic carbamate; optionally converting the cyclic carbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or salt, solvate or hydrate thereof.
  • the present invention provides a method for preparing a 1,2-aminoalcohol or
  • 1,2-aminothiol, or a salt, solvate or hydrate thereof the method comprising: reacting an alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate; deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the 1,2-aminoalcohol or
  • 1,2-aminothiol optionally converting the 1,2-aminoalcohol or 1,2-aminothiol into a salt, solvate or hydrate thereof; and optionally isolating the 1,2-aminoalcohol or 1,2-aminothiol or salt, solvate or hydrate thereof.
  • the alkenylamine is enantiopure and the reactions are stereo- and regioselective, such that the resulting 1,2-aminoalcohol or 1,2-aminothiol is chiral.
  • the alkenylamine is stereoisomerically pure and the reactions are stereo- and regioselective, such that the resulting 1,2-aminoalcohol or 1,2-aminothiol is stereoisomerically pure.
  • L is selected from the group consisting of:
  • R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 , R 42 , R 51 and R 52 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , R 41 and R 42 , and/or R 51 and R 52 , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R 11 and R 21 , R 12 and R 22 , R 21 and R 31 , R 22 and R 32 , R 31 and R 41 , R 32 and R 42 , R 41 and R 51
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 at each occurrence are independently selected from -H, -CN, -R 8 , -C(X)R 8 , -C(X)XR 8 , -C(R 8 ) 3 , -C(R 8 ) 2 XR 8 , -CR 8 (XR 8 ) 2 and -C(XR 8 ) 3 ; wherein X at each occurrence is independently selected from O, NH, NR 9 and S; and R 8 and R 9 at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, substituted heterocyclyl, substituted heterocyclyl, substituted heterocyclyl, substituted heterocyclyl, substituted hetero
  • Y is O.
  • the compound of Formula IV is selected from the group consisting of the compounds of Formula IVa, IVb and IVc:
  • the compound of Formula IV is selected from the group consisting of the compounds of Formula IVa and IVb.
  • the compound of Formula IV is selected from the group consisting of the compounds of Formula IVa', IVb' and IVc':
  • the compound of Formula IV is selected from the group consisting of the compounds of Formula IVa' and IVb'. In another preferred embodiment, the compound of Formula IV has the Formula IVa:
  • Y is O or S
  • R , R , R and R are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I;
  • R and R and/or R and R together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R 11 and R 21 and/or R 12 and R 22 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • the compound of Formula IV has the Formula IVa; wherein
  • R and R are -H, and R and R are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 12 and R 22 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • Y is O.
  • the compound of Formula IV has the Formula IVa; wherein Y is O or S;
  • R and R are -H, and R and R are each independently selected from the group consisting of -H, -N 3 , -OR 2 and -NR 3 R 4 , wherein R 2 , R 3 and R 4 at each occurrence are each independently selected from -H, -R 8 , -C(X)R 8 and -C(X)XR 8 ;
  • X at each occurrence is independently selected from O, NH, NR 9 and S; and R 8 and R 9 at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.
  • Y is O.
  • the compound of Formula IV has the Formula IVa; wherein Y is O or S;
  • R 11 and R 21 are -H
  • R 12 is -OH
  • R 22 is selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein
  • R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • Y is O.
  • the compound of Formula IV has the Formula IVa; wherein Y is O or S;
  • R 11 and R 21 are -H
  • R 12 and R 22 are -OH.
  • Y is O.
  • the compound of Formula IV has the Formula IVa; wherein Y is O or S;
  • R 11 , R 21 and R 22 are -H;
  • R 12 is -OH.
  • Y is O.
  • the compound of Formula IV has the Formula IVb:
  • Y is O or S
  • R , R , R , R , R and R are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 11 and R 12 , R 21 and R 22 , and/or R 31 and R 32 , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or alternatively R 11 and R 21 , R 12 and R 22 , R 21 and R 31 , and/or R 22 and R 32 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl,
  • Y is O.
  • the compound of Formula IV has the Formula IVb; wherein Y is O or S;
  • R 11 , R 21 and R 31 are -H
  • R 12 , R 22 and R 32 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R and R and/or R and R together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • Y is O.
  • the compound of Formula IV has the Formula IVb; wherein Y is O or S; R 11 , R 21 and R 31 are -H, and R 12 , R 22 and R 32 are each independently selected from the group consisting of -H, -N 3 , -OR 2 and -NR 3 R 4 , wherein R 2 , R 3 and R 4 at each occurrence are each independently selected from -H, -R 8 , -C(X)R 8 and -C(X)XR 8 ;
  • X at each occurrence is independently selected from O, NH, NR 9 and S;
  • R 8 and R 9 at each occurrence are independently selected from -H, alkyl, substituted alkyl, ⁇ alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.
  • Y is O.
  • the compound of Formula IV has the Formula IVb; wherein Y is O or S;
  • R 11 , R 21 and R 31 are -H; R 12 is -OH; and R 22 and R 32 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • Y is O.
  • the compound of Formula IV has the Formula IVb; wherein Y is O or S;
  • R 11 , R 21 and R 31 are -H;
  • R 12 and R 22 are -OH;
  • R 32 is selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein
  • R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • Y is O.
  • the compound of Formula IV has the Formula IVb; wherein Y is O or S;
  • R 11 , R 21 and R 31 are -H;
  • R 12 , R 22 and R 32 are -OH.
  • Y is O.
  • the compound of Formula IV has the Formula IVb; wherein Y is O or S;
  • R 11 , R 21 , R 31 and R 32 are -H;
  • R 12 and R 22 are -OH.
  • the compound of Formula IV has the Formula IVc:
  • Y is O or S
  • R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 and R 42 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , and/or R 41 and R 42 , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R 11 and R 21 , R 12 and R 22 , R 21 and R 31 , R 22 and R 32 , R 31 and R 41 , and/or R 32 and R 42 , together with the carbon atoms to which they are attached, form a cyclic group
  • Y is O.
  • the compound of Formula IV has the Formula IVc; wherein Y is O or S;
  • R 11 , R 21 , R 31 and R 41 are -H
  • R 12 , R 22 , R 32 and R 42 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I; or R 12 and R 22 , R 22 and R 32 , and/or R 32 and R 42 , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.
  • Y is O.
  • the compound of Formula IV has the Formula IVc; wherein Y is O or S; R 11 , R 21 , R 31 and R 41 are -H, and R 12 , R 22 , R 32 and R 42 are each independently selected from the group consisting of -H, -N 3 , -OR 2 and -NR 3 R 4 , wherein R 2 , R 3 and R 4 at each occurrence are each independently selected from -H, -R 8 , -C(X)R 8 and -C(X)XR 8 ; X at each occurrence is independently selected from O, NH, NR 9 and S; and R 8 and R 9 at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, heteroary
  • Y is O.
  • the compound of Formula IV has the Formula IVc; wherein Y is O or S;
  • R u , R 21 , R 31 and R 41 are -H;
  • R 12 is -OH
  • R 22 , R 32 and R 42 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for
  • Y is O.
  • the compound of Formula IV has the Formula IVc; wherein Y is O or S; R 11 , R 21 , R 31 and R 41 are -H; R 12 and R 22 are -OH; and
  • R 32 and R 42 are each independently selected from the group consisting of -H, -R 1 , -OR 2 , -SR 2 , -NR 3 R 4 , -NO 2 and -N 3 ; wherein R 1 , R 2 , R 3 and R 4 are as defined for Formula I.
  • Y is O.
  • the compound of Formula IV has the Formula IVc; wherein Y is O or S;
  • R 11 , R 21 , R 31 and R 41 are -H;
  • R 12 , R 22 , R 32 and R 42 are -OH.
  • Y is O. It will be appreciated that the compounds of Formula I, II, III and IV are contemplated as chemically feasible compounds.
  • the group L includes five or fewer spiro rings and/or fused rings. In another embodiment of the invention, the group L includes four or fewer spiro rings and/or fused rings. In another embodiment of the invention, the group L includes three or fewer spiro rings and/or fused rings. In another embodiment of the invention, the group L includes two or fewer spiro rings and/or fused rings. In another embodiment of the invention, the group L includes one or no spiro rings and/or fused rings. In another embodiment of the invention, the group L includes no spiro rings and/or fused rings.
  • the compound of Formula III may be deprotected to provide the compound of Formula IV using known methods. Such methods include, but are not limited to: reactions under alkaline conditions, for example with sodium hydroxide in ethanol at reflux temperature; reactions under acidic conditions, for example with 6N aqueous HCl at reflux temperature; and reaction with peroxides, for example LiOOH or H 2 O 2 ZLiOH.
  • the method further comprises reacting a compound of Formula II, as defined above, with a reaction metal, a source of ammonia and a hydride source to provide the compound of Formula I.
  • the invention also provides a compound of Formula IV, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.
  • the compound of Formula I is enantiopure and the resulting compound of Formula IV is chiral. If necessary, the compound of Formula I may be resolved into enantiomers using methods known to those persons skilled in the art.
  • the compound of Formula I is stereoisomerically pure and the resulting compound of Formula IV is stereoisomerically pure.
  • the present invention provides a method for preparing a 1,2-aminoalcohol or 1 ,2-aminothiol, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate; deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the 1,2-aminoalcohol or 1,2-aminothiol; optionally converting the 1,2-aminoalcohol or 1,2-aminothiol into a salt, solvate or hydrate thereof; and optionally isol
  • the halogen-substituted cyclic acetal or derivative thereof is enantiopure and the reactions are stereo- and regioselective, such that the resulting 1,2-aminoalcohol or 1,2-aminothiol is chiral.
  • the halogen-substituted cyclic acetal or derivative thereof is stereoisomerically pure and the reactions are stereo- and regioselective, such that the resulting 1,2-aminoalcohol or 1,2-aminothiol is stereoisomerically pure.
  • the alkenylamine is reacted with a halogen source, a base and a source of carbonate or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate.
  • a compound of Formula I is reacted with a source of carbonate or a source of carbon disulfide to provide a compound of Formula III.
  • the alkenylamine is reacted with a halogen source, a base and a source of carbonate to provide a cyclic carbamate.
  • the alkenylamine is reacted with a halogen source, a base and a source of carbon dioxide to provide a cyclic carbamate.
  • the alkenylamine is reacted with a halogen source, a base and a source of carbon disulfide to provide a cyclic dithiocarbamate.
  • a preferred embodiment of the fifth aspect provides a method for preparing a 1,2-aminoalcohol, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide to provide a cyclic carbamate; deprotecting the cyclic carbamate to provide the 1 ,2-aminoalcohol; optionally converting the 1,2-aminoalcohol into a salt, solvate or hydrate thereof; and optionally isolating the 1,2-aminoalcohol or salt, solvate or hydrate thereof.
  • the present invention provides the halogen-substituted cyclic acetal:
  • the halogen-substituted cyclic acetal has the following stereochemistry :
  • the present invention provides an alkenylamine selected from the group consisting of:
  • the alkenylamine is selected from the group consisting of:
  • the present invention provides a cyclic carbamate selected from the group consisting of:
  • the cyclic carbamate is selected from the group consisting of:
  • the cyclic carbamate is selected from the group consisting of:
  • the cyclic carbamate is selected from the group consisting of:
  • the functional groups of intermediate compounds may need to be protected by protecting groups.
  • Functional groups which it may be desirable to protect include, but are not limited to: hydroxyl; amino; and carboxylic acid groups.
  • Protecting groups may be added and removed in accordance with techniques that are well known to those persons skilled in the art. The use of protecting groups is described in, for example, J. W. F. McOmie (ed.),
  • the solvent is an aqueous solvent system, which typically comprises either water or a mixture of water and one or more suitable organic solvent.
  • the organic solvent may be miscible or immiscible with water.
  • the aqueous solvent system comprises a two phase solvent mixture and includes a phase transfer catalyst.
  • Suitable organic solvents include, but are not limited to: alcohols, for example methanol and ethanol; acetonitrile; dioxane; tetrahydrofuran; dimethyl formamide; and dimethyl sulfoxide.
  • the reaction may be carried out at ambient temperature.
  • the reaction mixture may be heated or cooled, using standard techniques.
  • the product compound may be isolated from the reaction mixture using standard techniques known in the art. Such techniques include, but are not limited to: filtration; solvent extraction; and evaporation.
  • the product compound may optionally be purified, using standard techniques known in the art, either as part of, or following isolation from the reaction mixture.
  • cyclic acetal compounds 1, 5, 9, 13, 17, and 21 were prepared using a literature procedure (Skaanderup, P. R.; Poulsen, C. S.; Hyldtoft, L.; J ⁇ rgensen, M. R.; Madsen, R. Synthesis 2002, 12, 1721-1727). Cyclic acetal 25 was prepared by an analogous procedure.
  • the solution was filtered through celite and concentrated under reduced pressure.
  • the filtrate was dissolved in /PrOH (4 mL) and filtered through cotton wool.
  • the solution was dry loaded on to silica gel and purified by gradient flash chromatography (DCM/EtOH/MeOH/30% aqueous NH 3 , from 25/2/2/1 to 5/2/2/1, v/v/v/v) to give the alkenylaniine 2 as the HCl salt (32 mg, 0.21 mmol, 95%).
  • (2S,3S)-l-Amino-pent-4-ene-2,3-diol (2) was also prepared using the following procedure.
  • halogenated cyclic acetal 1 (60.1 mg, 0.22 mmol) in a saturated solution OfNH 4 OAc in EtOH (5 mL) was added activated Zn (72.0 mg, 1.1 mmol), NaCNBH 3 (42 mg, 0.66 mmol) and 30% aqueous NH 3 (2 mL).
  • the mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure.
  • the residue was redissolved in water and purified directly by ion-exchange chromatography (Dowex H + ).
  • the product was eluted using 5- 15% aqueous NH 3 .
  • Alkenylamine 2 was obtained as the HCl salt (32 mg, 0.21 mmol, 95%).
  • the solution was filtered through celite and concentrated under reduced pressure.
  • the filtrate was dissolved in /PrOH (4 niL) and filtered through cotton wool.
  • the solution was dry loaded on to silica gel and purified by gradient flash chromatography (DCM/EtOH/MeOH/30% aqueous NH 3 , from 25/2/2/1 to 5/2/2/1, v/v/v/v) to give the alkenylamine 6 as the HCl salt (26 mg, 0.17 mmol, 91%).
  • (2S,3R)-l-Amino-pent-4-ene-2,3-diol (6) was also prepared using the following procedure. To a solution of halogenated cyclic acetal 5 (51.2 mg, 0.19 mmol) in a saturated solution OfNH 4 OAc inEtOH (4 mL) was added activated Zn (62 mg, 0.95 mmol), NaCNBH 3 (36.4 mg, 0.57 mmol) and 30% aqueous NH 3 (1.5 mL). The mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure. The residue was redissolved in H 2 O and purified directly by ion-exchange chromatography (Dowex H + ). The product was eluted using 5- 15% aqueous NH 3 . Alkenylamine 6 was obtained as the HCl salt (26 mg, 0.17 mmol, 91%).

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Abstract

L'invention porte sur un procédé pour préparer une alcénylamine, ou un sel, solvate ou hydrate de celui-ci. Le procédé comprend la réaction d'un acétal cyclique substitué par halogène ou d'un dérivé de celui-ci dans des conditions particulières pour fournir l'alcénylamine, qui peut être facultativement convertie en un sel, solvate ou hydrate de celui-ci. L'invention porte également sur un procédé de préparation d'un carbamate cyclique ou dithiocarbamate cyclique, ou d'un sel, solvate ou hydrate de celui-ci. Le procédé comprend la réaction d'une alcénylamine dans des conditions particulières pour fournir le carbamate cyclique ou le dithiocarbamate cyclique, qui peut être facultativement converti en un sel, solvate ou hydrate de celui-ci. L'invention porte également sur un procédé de préparation d'un 1,2-aminoalcool ou 1,2-aminothiol, ou d'un sel, solvate ou hydrate de celui-ci. Le procédé comprend la formation d'un carbamate cyclique ou d'un dithiocarbamate cyclique à partir d'une alcénylamine, et la déprotection du carbamate cyclique ou du dithiocarbamate cyclique pour fournir le 1,2-aminoalcool ou le 1,2-aminothiol, qui peut être facultativement converti en un sel, solvate ou hydrate de celui-ci.
PCT/NZ2009/000216 2008-10-09 2009-10-09 Procédés pour la préparation d'alcénylamines, de carbamates cycliques ou de dithiocarbamates, et d'aminoalcools ou d'aminothiols WO2010041964A1 (fr)

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Publication number Priority date Publication date Assignee Title
US10906904B2 (en) 2015-07-02 2021-02-02 Horizon Orphan Llc ADO-resistant cysteamine analogs and uses thereof
US11505550B2 (en) 2015-07-02 2022-11-22 Horizon Orphan Llc ADO-resistant cysteamine analogs and uses thereof

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