26 N.M.Xavier et al. RO, OR RO.OR RO. OR RO N-o OH MsCI OMs RO OH py 17 R=Ac or Piv py 18 19 HCI,EIOH/H2O or 00 HO HO OH (for R=Ac) 20a-c L-ido L-altro Scheme7L-Aldono-1.4-actones from Daldose perpivaloates and peracetates 3 Aldonolactones as Useful Chirons The use of aldonolactones for the preparation of carbasugars and iminosugars has been well explored and documented,particularly by Lundt's group [2-4,29-31]. Fleet has also given an overview of the utility of sugar lactones as synthons for biologically active compounds [5]and his research group has made major con- tributions to the synthesis of sugar mino acids from aldonolactones [32-34].We view here the s of C-gly ugar actants and related polymers that make use of aldono lactone as starting materials As shown in chapter,"Synthetic polymers from readily available monosacchar ides"by J.A.Galbis and M.G.Garcia-Martin,aldonolactones are useful monomeric materials for the synthesis of biodegradable polymers and bio-compatible polymers for medicinal applications. 3.1 Synthesis of Surfactants and Polymers Among the aldonolactone-based surfactants are aldonolactone-linked fatty esters which have been prepared by selective acylation of unprotected aldono-1.4-lac- tones or aldono-1,5-lactones.One of the first reported examples of this type of surfactant was applied to the enzymatic synthesis of 6-0-alkanoylgluconolactones [35].Thus,6-0-decanoyl-and 6-0-dodecanoyl-derivatives(21a and 21b,respec tively,Scheme 8)were obtained in 26-27%yield by esterification of glucono-1,5- lactone (1)at C-6 with the corresponding 2.2.2-trichloroethyl carboxylate in the pancreatic lipase (PPL)as catalyst.Com ounds 21a.b are in water at 96C but prec cipitate n cooled to 3-37C.NMR GC-MS analysis after dis tion and preci the prese ence in th mixture of compound 21b,the glucono-1,4-lactone-derived ester 22,and the
3 Aldonolactones as Useful Chirons The use of aldonolactones for the preparation of carbasugars and iminosugars has been well explored and documented, particularly by Lundt’s group [2–4, 29–31]. Fleet has also given an overview of the utility of sugar lactones as synthons for biologically active compounds [5] and his research group has made major contributions to the synthesis of sugar amino acids from aldonolactones [32–34]. We review here the syntheses of C-glycosyl compounds, L-sugars, aza- and thiosugars, natural products and of surfactants and related polymers that make use of aldonolactones as starting materials. As shown in chapter, “Synthetic polymers from readily available monosaccharides” by J.A. Galbis and M.G. Garcia-Martin, aldonolactones are useful monomeric materials for the synthesis of biodegradable polymers and bio-compatible polymers for medicinal applications. 3.1 Synthesis of Surfactants and Polymers Among the aldonolactone-based surfactants are aldonolactone-linked fatty esters which have been prepared by selective acylation of unprotected aldono-1,4-lactones or aldono-1,5-lactones. One of the first reported examples of this type of surfactant was applied to the enzymatic synthesis of 6-O-alkanoylgluconolactones [35]. Thus, 6-O-decanoyl- and 6-O-dodecanoyl- derivatives (21a and 21b, respectively, Scheme 8) were obtained in 26–27% yield by esterification of glucono-l,5- 1actone (1) at C-6 with the corresponding 2,2,2-trichloroethyl carboxylate in the presence of porcine pancreatic lipase (PPL) as catalyst. Compounds 21a,b are soluble in water at 90–96C but precipitate when cooled to 30–37C. NMR and GC-MS analysis after dissolution and precipitation indicated the presence in the mixture of compound 21b, the glucono-l,4-1actone-derived ester 22, and the O OR RO RO RO OR OH OR RO RO N OH RO OMs OR RO RO N RO O O HO OH HO OH MsCl 17 R = Ac or Piv D-galacto D-gluco D-manno py HCl, EtOH/H2O or NH2OH.HCl (for R = Ac) py a) MeCN, H2O b) HCl, EtOH/H2O (for R = Ac) 18 19 20a-c L-altro L-ido L-gulo NH2OH or Scheme 7 L-Aldono-1,4-lactones from D-aldose perpivaloates and peracetates 26 N.M. Xavier et al
Carbohydrate-Based Lactones:Synthesis and Applications OH H RCO2CH2CCla H00 PPL R=( 21a R=(CH)aCHa (27% 21b R=(CH2)(26%) (CH2)1oCH3 COH HO- 0 LOCO(CH2)10CHa 22 Scheme 8 Enzymatic synthesis of 6-0-alkanoylgluconolactones g the major r compound.This ation of 21b occurs with hydrolysis of the lactone moiety giving a more soluble mixture of compounds that are more appropriate for detergent applications than the dodecanoylglucono-1.5-lactone itself. Acylation of D-glucono-1,4-lactone and D-glucono-1,5-lactone with N-(11-unde- cenoyl)-1.3-thiazolidine-2-thione in the presence of triethylamine gave 6-0-unde cenoyl ester as the single product.In the case of the 1.5-lactone,isomerization to the 1.4-lactone-derived ester was observed,and quantitative conversion was attained when sodium hydride was used as base.In contrast with the expected regioselec acylatic of L -14l cton proc only at OH with vely,the route employing Candid antartica and an ester.proved to be more efficient,affording only 6-0-acylated-1,4-lactone derivatives in yields up to 76 and 85%,by acylation of p-glucono-1,5-lactone and L-galactono-1,4-lactone,respectively.The conversion was shown to increase with the electron-withdrawing character of the ester.while acids proved to be virtually unreactive as acylating agents [36]. Another type of amphiphilic-like structure in which an aldonolactone moiety is present was prepared by ac cetalization of D-glucono-1.4-lactone(24)and p-glucono 1.5-lactone (1)with dode anal or tetrade tha an al in the enc of me ulfo (Scheme 9)[37] lac I der 26a.bin optim zed yiel ds up to60 -79% acetal A mecha sm for t出 on wa proposed,involving a hemi-orthoester(25)as a key intermediate in the addition to the aldehyde.Then,opening of an intermediate bicyclic-fused system and concom- itant cyclization led to the acetal 26. In the context of the synthesis of carbohydrate-based amphiphilic (alkylsulfanyl) polyols,Beaupere and co-workers explored the access to 5-and 6-alkylsulfanyl
acyclic dodecanoylgluconic acid 23, the latter being the major compound. This demonstrates that dissolution of 21b occurs with hydrolysis of the lactone moiety giving a more soluble mixture of compounds that are more appropriate for detergent applications than the dodecanoylglucono-1,5-lactone itself. Acylation of D-glucono-1,4-lactone and D-glucono-1,5-lactone with N-(11-undecenoyl)-1,3-thiazolidine-2-thione in the presence of triethylamine gave 6-O-undecenoyl ester as the single product. In the case of the 1,5-lactone, isomerization to the 1,4-lactone-derived ester was observed, and quantitative conversion was attained when sodium hydride was used as base. In contrast with the expected regioselectivity at OH-6, acylation of L-galactono-1,4-lactone proceeded only at OH- 2 although with a rather low yield (ca. 20%). Alternatively, the enzymatic route, employing Candida antartica and an ester, proved to be more efficient, affording only 6-O-acylated-1,4-lactone derivatives in yields up to 76 and 85%, by acylation of D-glucono-1,5-lactone and L-galactono-1,4-lactone, respectively. The conversion was shown to increase with the electron-withdrawing character of the ester, while acids proved to be virtually unreactive as acylating agents [36]. Another type of amphiphilic-like structure in which an aldonolactone moiety is present was prepared by acetalization of D-glucono-1,4-lactone (24) and D-glucono- 1,5-lactone (1) with dodecanal or tetradecanal in the presence of methanesulfonic acid (Scheme 9) [37]. Both lactone isomers led to 1,4-lactone acetal derivatives 26a, b in optimized yields up to 60–79%. A mechanism for the ring contraction was proposed, involving a hemi-orthoester (25) as a key intermediate in the addition to the aldehyde. Then, opening of an intermediate bicyclic-fused system and concomitant cyclization led to the acetal 26. In the context of the synthesis of carbohydrate-based amphiphilic (alkylsulfanyl) polyols, Beaupe`re and co-workers explored the access to 5- and 6-alkylsulfanyl derivatives of pentono- and hexonolactones and their corresponding 1-(alkylsulfanyl) pentitol or 1-(alkylsulfanyl)hexitol [38, 39]. Bromolactones 27 and 30 were treated O O OH HO HO HO PPL RCO2CH2CCl3 R = (CH2)8CH3 or (CH2)10CH3 O O O HO HO HO R O 1 21a R = (CH2)8CH3 21b R = (CH2)10CH3 O O HO OH OH O O (CH2)10CH3 22 CO2H OH HO OH OH OCO(CH2)10CH3 23 (27%) (26%) Scheme 8 Enzymatic synthesis of 6-O-alkanoylgluconolactones Carbohydrate-Based Lactones: Synthesis and Applications 27
28 N.M.Xavier et al. HO OH OH +RCHO HO C HO OH OH OH R OH HO. 0 -H'cat. 26aR=(CH10C4(33-79%24 26bR=(CH)12CHh(34-60% etalization of pglucono-1.4-lactone and pglucono-1.5-lactone with dodecanal or RS RSH,NaH OH HO 27 D-ribo 29 b-xylo OHOH RSH.NaH 0 NaBH.EtOH HO BS OH OHOH OH 31 Scheme 10Amphiphilic (alkylsulfanyladonolactones and corresponding alditols with alkanethiol in the presene of sodium hydride (Scheme 10)giving comound 28 and 31,respectively,in good yields(72-95%).Subsequent lactone reduction with NaBHa provided the 1-S-alkyl-1-thio-alditol derivatives 29 and 32,respec tively.Physico-chemical studies demonstrated surface activity for all compounds 28,except for the D-ribono derivatives for which no critical micellar concentration (CMC)value was detected [401.Apart from the lyxitol series.the pentitol deriva- ore efficient in reducing the surface tension than their their cvclic counterparts 20.pas ploperes ol 28 and 29 were alsc of the ave and ther als exeet for the rics ofcne.Th
with alkanethiol in the presence of sodium hydride (Scheme 10) giving compounds 28 and 31, respectively, in good yields (72–95%). Subsequent lactone reduction with NaBH4 provided the 1-S-alkyl-1-thio-alditol derivatives 29 and 32, respectively. Physico-chemical studies demonstrated surface activity for all compounds 28, except for the D-ribono derivatives for which no critical micellar concentration (CMC) value was detected [40]. Apart from the lyxitol series, the pentitol derivatives of type 29 were shown to be more efficient in reducing the surface tension than their cyclic counterparts 28. The mesophasic properties of 28 and 29 were also evaluated [41]. Most of the compounds gave lyotropic and thermotropic liquid crystals, except for the series of D-ribonolactones. This singular behavior for the O O OH HO HO HO O O HO OH OH OH O OH O OH OH HO O OH OH HO HO HO O OH O OH OH O OH R H O O O OH OH O R H O O O OH OH O R – H+ cat. RCHO R = (CH2)10CH3 or (CH2)12CH3 1 24 25 – H2O 26a R = (CH2)10CH3 (33-79%) 26b R = (CH2)12CH3 (34-60%) – H+ – H+ + H+ + H+ + RCHO Scheme 9 Acetalization of D-glucono-1,4-lactone and D-glucono-1,5-lactone with dodecanal or tetradecanal O O HO OH HO Br O O HO OH Br O O HO OH RS O O HO OH HO SR RS OH OH OH OH RS OH OH OH OH OH RSH, NaH RSH, NaH NaBH4, EtOH NaBH4, EtOH 27 28 29 30 31 32 D-ribo D-xylo D-arabino R = C6H13 8H17 C10H21 C C 12H25 D-galacto D-manno R = C8H17 9H19 10H21 11H23 C C C C 12H25 Scheme 10 Amphiphilic (alkylsulfanyl)aldonolactones and corresponding alditols 28 N.M. Xavier et al
Carbohydrate-Based Lactones:Synthesis and Applications 29 ribono derivatives 28 was ascribed to the position of the vicinal hydroxyl groups which are in the same side of the cycle,favoring intramolecular hydrogen bonding. It has been known for more than 50 years that carbohydrate lactones undergo ring opening by amines.Using long chain primary amines gives access to amphi- philic structures that are emulsifying agents [42.43]or liquid crystals [44-47].The preparation of N-arylgluconoamides and N-alkylgluconoamides by opening of p-glucono-1.5-lactone,and their subsequent conversion into thiogluconamide deri- r.Some amphiphilia have the propensity leading to di erent structural morphologies containing aldonoamide moieties at their molecular surfaces have been prepared by coupling polyamine dendrimers with 1,5-D-glucono-1,4-lactone [53-55].Such macromolecules are shown to behave as unimolecular micelles in water able to solubilize hydrophobic compounds in the dendritic cavities [55].Highly enantio- selective ketone reduction have been carried out in the presence of these systems. In recent work [56]aldonoamides(33.34)have been synthesized in moderate to me 1).In addit een obt nt of the against M.tuberculosis.Some ribonoamides were also active against Staphylococ cus aureus.The activities increased somewhat with the elongation of their hydro- carbon chains. The use of carbohydrates as raw materials for the generation of polymers has attracted particular interest in the last two decades not only because of concerns material (for OH CHj(CH.NH(CHz).NH2 OHOH HO NH(CH2).NH(CH2)-CH3 H00 m=7,9,11.13 6md 1 n=2.3 33 CHa(CH2)-NH(CH).NHz o.o NH(CHz).NH(CH2).CHa 6H8 HO OH 34 NzH.H.O↓ CHa(CH2-CHO NHNH2 6H0 m=6,8 NE 6H0 (CH2)mCH3 35 36 Scheme 11 Amphiphilic compounds by ring-opening of aldonolactones
ribono derivatives 28 was ascribed to the position of the vicinal hydroxyl groups which are in the same side of the cycle, favoring intramolecular hydrogen bonding. It has been known for more than 50 years that carbohydrate lactones undergo ring opening by amines. Using long chain primary amines gives access to amphiphilic structures that are emulsifying agents [42, 43] or liquid crystals [44–47]. The preparation of N-arylgluconoamides and N-alkylgluconoamides by opening of D-glucono-1,5-lactone, and their subsequent conversion into thiogluconamide derivatives, are reported [48]. Some amphiphilic alkyl aldonamides and diacetylenic aldonamides have the propensity to aggregate into supramolecular assemblies, leading to different structural morphologies [49–52]. Amphiphilic glycodendrimers containing aldonoamide moieties at their molecular surfaces have been prepared by coupling polyamine dendrimers with 1,5-D-glucono-1,4-lactone [53–55]. Such macromolecules are shown to behave as unimolecular micelles in water able to solubilize hydrophobic compounds in the dendritic cavities [55]. Highly enantioselective ketone reduction have been carried out in the presence of these systems. In recent work [56] aldonoamides (33, 34) have been synthesized in moderate to good yields by addition of long-chain N-monoalkylated diamines to D-glucono-1,5- lactone 1 or D-ribono-1,4-lactone 14 (Scheme 11). In addition, hydrazones 36 have been obtained by treatment of the intermediate ribonohydrazide 35 with octanal or decanal. All compounds derived from ribonolactone showed moderate activity against M. tuberculosis. Some ribonoamides were also active against Staphylococcus aureus. The activities increased somewhat with the elongation of their hydrocarbon chains. The use of carbohydrates as raw materials for the generation of polymers has attracted particular interest in the last two decades not only because of concerns related with sustainability and biocompatibility, but also due to the unique mechanical and physical properties that the sugar units may provide to the material (for O O OH HO HO HO O O HO OH HO HO NH(CH2)nNH(CH2)mCH3 OH O OH OH OH HO NH(CH2)nNH(CH2)mCH3 O OH OH OH N2H4⋅H2O 2 O OH OH OH HO NHNH HO NH O OH OH OH N H (CH2)mCH3 1 14 CH3(CH2)mNH(CH2)nNH2 m = 7, 9, 11, 13 n = 2, 3 CH3(CH2)mNH(CH2)nNH2 CH3(CH2)mCHO m = 6, 8 33 34 35 36 Scheme 11 Amphiphilic compounds by ring-opening of aldonolactones Carbohydrate-Based Lactones: Synthesis and Applications 29
30 N.M.Xavier et al. reviews on carbohydrate-based polymers see [57-59)).The hydrophilic sugar moiety contributes to the specific three-dimensional structure of the polymer and increases its hydrophilicity and water solubility.Due to their particular character istics,glycopolymers have found interesting dete rgents, urface modifiers and also medical field as biomat and fo terials for satalyssoadon by r gene delivery systems(See Quignard,Di Renzo and Guibal,and chapter,"Synthetic polymers from readily available monosaccharides",by Galbis and Garcia-Martin). One of the approaches employed to achieve sugar-based polymers consists in the preparation of monomers comprising the sugar moiety and a polymerizable double bond Aldonolactones can be useful starting materials for this type of monomers, allowing the introduction of the polymerizable part through selective monofunctio nalization of the lactone.without the use of pre otectins g group The nection of oth parts an be acc omplished.fo ample h link g e of the first repored examplesapplying this approach involved the ddition of an aminoalkyl ammonium methacrylate salt,derived from a diamine and methacrylic acid,to D-glucono-1.5-lactone 1 (Scheme 12).The resulting ionic monomers 37 were then subiected to homopolymerization in the presence of a free-radical initia- tor to give the corresponding polymers 38 in good yields.Studies of the viscosity of their aqueous solution showed a decrease of this parameter when increasing the concentration.proving their polyelectrolyte nature.NMR analysis of polymers 38 evealed their predon minant svndiotatic structure.The m mer 37a (n=2)was als cop ith 1-vinylpyrrolidin-2-one and methacrylamide,affording Aldonolactones serve as suitable monomers for the generation of homo-and copolymers,especially through ring-opening polymerization (ROP).Among them are the carbohydrate-analogs of g-caprolactone.ie..aldono-1,6-lactones.The first example of such derivatives and further ROP was reported by Galbis and co-workers [61],see also chapter,"Synthetic polymers from readily available monosaccharides" HaC OHOH 1 NH(CH2)NHaoC HO m=2,5.8 TMEDA.nt 37a-c (76-92%1 K2S208 n HO NH(CHa.NHaO.CH, OHOH O 38a-c Scheme 12 Gluconolactone-derived vinyl monomers and their polymerizatior
reviews on carbohydrate-based polymers see [57–59]). The hydrophilic sugar moiety contributes to the specific three-dimensional structure of the polymer and increases its hydrophilicity and water solubility. Due to their particular characteristics, glycopolymers have found interesting applications as flocculating agents, detergents, surface modifiers, and also in the biomedical field as biomaterials for tissue regeneration, as drugs, and for gene delivery systems (See chapter, “From natural polysaccharides to materials for catalysis, adsorption and remediation”, by Quignard, Di Renzo and Guibal, and chapter, “Synthetic polymers from readily available monosaccharides”, by Galbis and Garcia-Martin). One of the approaches employed to achieve sugar-based polymers consists in the preparation of monomers comprising the sugar moiety and a polymerizable double bond. Aldonolactones can be useful starting materials for this type of monomers, allowing the introduction of the polymerizable part through selective monofunctionalization of the lactone, without the use of protecting groups. The connection of both parts can be accomplished, for example, through amide linkages. One of the first reported examples applying this approach [60] involved the addition of an aminoalkyl ammonium methacrylate salt, derived from a diamine and methacrylic acid, to D-glucono-1,5-lactone 1 (Scheme 12). The resulting ionic monomers 37 were then subjected to homopolymerization in the presence of a free-radical initiator to give the corresponding polymers 38 in good yields. Studies of the viscosity of their aqueous solution showed a decrease of this parameter when increasing the concentration, proving their polyelectrolyte nature. NMR analysis of polymers 38 revealed their predominant syndiotatic structure. The monomer 37a (n ¼ 2) was also copolymerized with 1-vinylpyrrolidin-2-one and methacrylamide, affording water-soluble copolymers. Aldonolactones serve as suitable monomers for the generation of homo- and copolymers, especially through ring-opening polymerization (ROP). Among them are the carbohydrate-analogs of e-caprolactone, i.e., aldono-1,6-lactones. The first example of such derivatives and further ROP was reported by Galbis and co-workers [61], see also chapter, “Synthetic polymers from readily available monosaccharides” HO NH(CH2)nNH3 OH O OH OH CO OH 2 CH3 H3C O2C K2S2O8 HO NH(CH2)nNH3 OH O OH OH OH H2 C O2CH3 H3C 1 m = 2, 5, 8 37a–c NH3(CH2)mNH2 TMEDA, rt or AAPDH or AIBN 70 °C 38a–c n (76–92%) Scheme 12 Gluconolactone-derived vinyl monomers and their polymerization 30 N.M. Xavier et al