Synthesis of Novel 8,14‐Secoursane Derivatives: Key Intermediates for the Preparation of Chiral Decalin Synthons from Ursolic Acid

The novel 8,14‐secoursatriene derivative 6 was synthesized starting from ursolic acid ( 1 ) via methyl esterification of the 17‐carboxylic acid group and benzoylation of the 3‐hydroxy group (→ 2 ; Scheme 1), ozone oxidation of the C(12)?C(13) bond (→ 3 ), dehydrogenation with Br₂/HBr (→ 4 ), enol acetylation of the resulting carbonyl group (→ 5 ; Scheme 2), and ring‐C opening with the aid of UV light (→ 6 ). Ring‐C‐opened dienone derivative 7 of ursolic acid was also obtained via selective hydrolysis of 6 (Scheme 2). Both compounds 6 and 7 are key intermediates for the preparation of chiral decalin synthons from ursolic acid.     

Mono- and Dialkylation of Derivatives of (1R, 2S)-2-Hydroxycyclopentanecarboxylic Acid and -cyclohexanecarboxylic acid via bicyclic dioxanones: Selective generation of three contiguous stereogenic centers on a cyclohexane ring

Ethyl (1R, 2S)-2-hydroxycyclopentanecarboxylate and -cyclohexanecarboxylate ( 1a and 2a , respectively) obtained in 40 and 70% yield by reduction of 3-oxocyclopentanecarboxylate and cyclohexanecarboxylate, respectively (Scheme 2), with non-fermenting yeast, are converted to bicyclic dioxanone derivatives 3 and 4 with formaldehyde, isobutyraldehyde, and pivalaldehyde (Scheme 3). The Li-enolates of these dioxanones are alkylated (→ 5a – 5i , 5j , 6a – 6g ), hydroxyalkylated (→ 51, m, 6d, e ), acylated (→ 5k, 6c ) and phenylselenenylated (→ 7 – 9 ) with usually high yields and excellent diastereoselectivities (Scheme 3, Tables and 2). All the major isomers formed under kinetic control are shown to have cis-fused bicyclic structures. Oxidation of the seleno compounds 7–9 leads to α, β-unsaturated carbonyl derivatives 10 – 13 (Scheme 3) of which the products 12a – c with the C?C bond in the carbocyclic ring (exocyclic on the dioxanone ring) are most readily isolated (70–80% from the saturated precursors). Michael addition of Cu(I)-containing reagents to 12a – c and subsequent alkylations afford dioxanones 14a – i and 16a – d with trans-fused cyclohoxane ring (Scheme 4). All enolate alkylations are carried out in the presence of the cyclic urea DMPU as a cosolvent. The configuration of the products is established by NMR measurements and chemical correlation. Some of the products are converted to single isomers of monocyclic hydroxycyclopentane ( 17 – 19 ) and cyclohexane derivatives ( 20 – 23 ; Scheme 5). Possible uses of the described reactions for EPC synthesis are outlined. The observed steric course of the reactions is discussed and compared with that of analogous transformations of monocyclic and acyclic derivatives.     

Fused 1,2‐Dithioles. Part VII

The 1,2‐dithiolosultam derivative 14 was obtained from the (α‐bromoalkylidene)propenesultam derivative 9 (Scheme 1). Regioselective cleavage of the two ester groups (→ 1b or 2b ) allowed the preparation of derivatives with different substituents at C(3) in the dithiole ring (see 27 and 28 ) as well as at C(6) in the isothiazole ring (see 17 – 21 ; Scheme 2). Curtius rearrangement of the 6‐carbonyl azide 21 in Ac₂O afforded the 6‐acetamide 22 , and saponification and decarboxylation of the latter yielded ‘sulfothiolutin’ ( 30 ). Hydride reductions of two of the bicyclic sultams resulted in ring opening of the sultam ring and loss of the sulfonyl group. Thus the reduction of the dithiolosultam derivative 14 yielded the alkylidenethiotetronic acid derivative 33 (tetronic acid=furan‐2,4(3H,4H)‐dione), and the lactam‐sultam derivative 10 gave the alkylidenetetramic acid derivative 35 (tetramic acid=1,5‐dihydro‐4‐hydroxy‐2H‐pyrrol‐2‐one) (Scheme 3). Some of the new compounds ( 14, 22, 26 , and 30 ) exhibited antimycobacterial activity. The oxidative addition of 1 equiv. of [Pt(η²‐C₂H₄)L₂] ( 36a , L=PPh₃; 36b , L=1/2 dppf; 36c , L=1/2 (R,R)‐diop) into the S? S bond of 14 led to the cis‐(dithiolato)platinum(II) complexes 37a – c . (dppf=1,1′‐bis(diphenylphosphino)ferrocene; (R,R)‐diop={[(4R,5R)‐2,2‐demithyl‐1,3‐dioxolane‐4,5‐diyl]bis(methylene)}bis[diphenylphosphine]).     

The chemistry of thujone. IX. Thujone as a chiral synthon for the synthesis of optically active steroid analogues. The vinylpicoline route

The thujone-derived enone 1 , upon base-catalyzed reaction with 2-methyl-6-vinylpyridine is converted to the pyridine analogue 5 (Scheme 1). Catalytic reduction of the latter to 6 generates two new centers of chirality which eventually become C(8) and C(14) in the ultimate synthetic steroid analogue 12 . An X-ray analysis of 6 establishes the structure and absolute configuration so as to determine its suitability in subsequent synthetic studies. The acetal derivative 7 , via Birch reduction, hydrolysis, and internal aldol cyclization, is converted into the cyclohexenone analogue 10 (Scheme 2). This ‘one-pot’ process affords an efficient conversion of the pyridine ring into a cyclohexenone system required for A-ring construction of the steroid skeleton. Finally, conversion of 10 , via the unsaturated diketone 11 , provides the chiral steroid analogue 12 .     

Efficient Synthesis of (−)‐(R)‐Muscone by Enantioselective Protonation

A new synthesis of (?)‐(R)‐muscone ((R)‐ 1 ) by means of enantioselective protonation of a bicyclic ketone enolate as the key step (see 6 →(S)‐ 4 in Scheme 2) is presented. The C₁₅ macrocyclic system is obtained by ozonolysis (Scheme 7).     

Domino‐Heck Reactions of Carba‐ and Oxabicyclic,Unsaturated Dicarboximides: Synthesis of Aryl‐Substituted,Bridged Perhydroisoindole Derivatives

The C? C coupling of the two bicyclic, unsaturated dicarboximides 5 and 6 with aryl and heteroaryl halides gave, under reductive Heck conditions, the C‐aryl‐N‐phenyl‐substituted oxabicyclic imides 7a – c and 8a – c (Scheme 3). Domino‐Heck C? C coupling reactions of 5, 6 , and 1b with aryl or heteroaryl iodides and phenyl‐ or (trimethylsilyl)acetylene also proved feasible giving 8, 9 , and 10a – c , respectively (Scheme 4). Reduction of 1b with LiAlH₄ (→ 11 ) followed by Heck arylation and reduction of 5 with NaBH₄ (→ 13 ) followed by Heck arylation open a new access to the bridged perhydroisoindole derivatives 12a , b and 14a , b with prospective pharmaceutical activity (Schemes 5 and 6).     

Photocycloaddition of Cyclohex‐2‐enones to 2‐Methylbut‐1‐en‐3‐yne

Irradiation (350 nm) of 2‐alkynylcyclohex‐2‐enones 1 in benzene in the presence of an excess of 2‐methylbut‐1‐en‐3‐yne ( 2 ) affords in each case a mixture of a cis‐fused 3,4,4a,5,6,8a‐hexahydronaphthalen‐1(2H)‐one 3 and a bicyclo[4.2.0]octan‐2‐one 4 (Scheme 2), the former being formed as main product via 1,6‐cyclization of the common biradical intermediate. The (parent) cyclohex‐2‐enone and other alkylcyclohex‐2‐enones 7 also give naphthalenones 8 , albeit in lower yields, the major products being bicyclo[4.2.0]octan‐2‐ones (Scheme 4). No product derived from such a 1,6‐cyclization is observed in the irradiation of 3‐alkynylcyclohex‐2‐enone 9 in the presence of 2 (Scheme 4). Irradiation of the 2‐cyano‐substituted cyclohexenone 12 under these conditions again affords only traces of naphthalenone 13 , the main product now being the substituted bicyclo[4.2.0]oct‐7‐ene 16 (Scheme 5), resulting from [2+2] cycloaddition of the acetylenic C−C bond of 2 to excited 12 .     

Synthesis of 3‐Aminotropones from N‐Boc‐Protected Furan‐2‐amine (=tert‐Butyl Furan‐2‐ylcarbamate; Boc=(tert‐Butoxy)carbonyl) by Cycloaddition Reactions and Subsequent Rearrangement

The 3‐aminotropones (=3‐aminocyclohepta‐2,4,6‐trien‐1‐ones) 4 were prepared in two steps by i) a [4+3] cycloaddition reaction between a conveniently substituted α,α′‐dihalo ketone 1 and a furan‐2‐amine derivative 2 functionalized at C(2) by a protected amino group (→ 3 ), and ii) a base‐induced molecular rearrangement of the cycloadduct 3 via cleavage of the O‐bridge. A mechanism for the formation of 3‐aminotropones is proposed on the basis of the initial deprotonation of the [(tert‐butoxy)carbonyl]amino (BocNH) group of 3 , followed by O‐bridge opening, an acid–base equilibrium, and finally an alkoxyaluminate elimination to afford the conjugated stable troponoid system (Scheme 7).     

Formation of Diastereoisomerically Pure Oxazaphospholes and Their Reaction to Chiral Phosphane‐Borane Adducts

Starting with achiral phosphines and (1S,2S)‐2‐(methylamino)‐1‐phenylpropan‐1‐ol ((+)‐pseudoephedrine) or (1R,2S)‐2‐(methylamino)‐1‐phenylpropan‐1‐ol ((−)‐ephedrine), as chiral auxiliaries, diastereoisomerically pure oxazaphospholes were prepared (Scheme 1). The configuration at the P‐atom is controlled by the configuration at the Ph‐substituted C(1) of (+)‐pseudoephedrine or (−)‐ephedrine, respectively. This was confirmed by X‐ray crystal‐structure analyses of two intermediate compounds in the synthesis route to the chiral triarylborane‐phosphane adducts.     

Enantioselective Nucleophilic Aromatic Substitution with Small‐Molecule Chiral Selectors

Small‐molecule rationally designed chiral selectors have been shown to influence the stereochemical outcome of a variety of organic transformations. For instance, in a recent report, we demonstrated that a chiral selector (in conjunction with an achiral phase‐transfer catalyst) could selectively inhibit one enantiomer of electron‐deficient aromatic amides from forming Meisenheimer adducts (Scheme 2). We now extend this methodology to performing enantioselective nucleophilic aromatic substitutions. Initial studies involved biphasic kinetic resolutions with a chiral selector in conjunction with an achiral phase‐transfer catalyst (Scheme 3). The results are consistent with previous data taken for biphasic reactions (e.g., Scheme 1) where the chiral selector effectively shields the more highly complexed enantiomer from reaction. With neutral nucleophiles such as amines, the enantioselective nucleophilic aromatic substitutions can also be conducted in single‐phase systems. Several examples are given.     

Synthesis of N-Acetylallosamine-Derived Disaccharides

The protected disaccharide 44 , a precursor for the synthesis of allosamidin, was prepared from the glycosyl acceptor 8 and the donors 26–28 , best yields being obtained with the trichloroacetimidate 28 (Scheme 6). Glycosidation of 8 or of 32 by the triacetylated, less reactive donors 38–40 gave the disaccharides 46 and 45 , respectively, in lower yields (Scheme 7). Regioselective glycosidation of the diol 35 by the donors 38–40 gave 42 , the axial, intramolecularly H-bonded OH? C(3) group reacting exclusively (Scheme 5). The glycosyl acceptor 8 was prepared from 9 by reductive opening of the dioxolane ring (Scheme 3). The donors 26–28 were prepared from the same precursor 9 via the hemiacetal 25 . To obtain 9 , the known 10 was de-N-acetylated (→ 18 ), treated with phthalic anhydride (→ 19 ), and benzylated, leading to 9 and 23 (Schemes 2 and 3). Saponification of 23 , followed by acetylation also gave 9 . Depending upon the conditions, acetylation of 19 yielded a mixture of 20 and 21 or exclusively 20 . Deacetylation of 20 led to the hydroxyphthalamide 22 . De-N-acetylation of the 3-O-benzylated β-D -glycosides 11 and 15 , which were both obtained from 10 , was very sluggish and accompanied by partial reduction of the O-allyl to an O-propyl group (Scheme 2). The β-D -glycoside 30 behaved very similarly to 11 and 15 . Reductive ring opening of 31 , derived from 29 , yielded the 3-O-acetylated acceptor 32 , while the analogous reaction of the β-D -anomer 20 was accompanied by a rapid 3-O→4-O acyl migration (→ 34 ; Scheme 4). Reductive ring opening of 21 gave the diol 35 . The triacetylated donors 38–40 were obtained from 20 by debenzylidenation, acetylation (→ 36 ), and deallylation (→ 37 ), followed by either acetylation (→ 38 ), treatment with Me₃SiSEt (→ 39 ), or Cl₃CCN (→ 40 ).     

Tandem Inter [4+2]/Intra [3+2] Cycloadditions of Nitroalkenes. Application to the Synthesis of Aminocarbasugars

The tandem inter [4+2]/intra [3+2] cycloaddition of nitroalkenes in the bridged mode was applied to the stereoselective synthesis of β‐D ‐4‐amino‐2,4‐dideoxycarbagulose, a representative aminocarbasugar. The synthesis required only five steps from known materials and delivered the protected aminocarbasugar (−)‐ 20 in excellent yield (see Scheme 9). The success of the synthetic sequence relies on 1) the ability to incorporate O‐substituents at the nitroalkene moiety, 2) the identification of a suitably modified chiral dienophile, and in particular 3) the development of specific experimental conditions and protocols that allow for the formation and isolation of the highly sensitive nitroso acetals. The reduction of the C(1) carbonyl group of (+)‐ 19 gave unexpected stereoselectivity, which could be rationalized by a conformational inversion of the substrate (see Scheme 11).     

Dichloro[TADDOLato(2−)-O,O′]titanium/Dichlorobis[1-methylethoxy]titanium-Mediated,Highly Diastereo- and Enantioselective Additions of Silyl Enol Ethers to Nitro Olefins and [3+2] Cycloadditions of Primary Adducts to Acetylenes

The diastereoselective, Ti-Lewis-acid-mediated, low-temperature addition of silyl enol ethers to 1-aryl-2-nitroethenes (Scheme 1) occurs enantioselectively with dichloro[TADDOLato(2−)-O,O′]titanium 3 (TADDOL=α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanol) (Scheme 2). At least 3 equiv. of Lewis acid are required for high conversions (yields). However, the chiral Lewis acid 3 can be `diluted' with the achiral Cl₂Ti(OCHMe₂)₂ analog (ratio 1 : 2.5), with hardly any loss of enantioselectivity! Both, the primary (4+2) cycloadducts ( B , 9 ) and the γ-nitro ketones ( A , 1a – h , 5 , 7 ), formed by hydrolysis, can be isolated in good yields and with high configurational purities (Schemes 3 and 4, and Table 1). The relative and absolute configurations (2S,1′R) of the products 1 from cyclohexanone silyl enol ether and 1-aryl(including 1-heteroaryl)-2-nitroethenes (obtained with (R,R)-TADDOLate) are assigned by NMR spectroscopy, and optical comparison and correlation with literature data, as well as by anomalous-dispersion X-ray crystal-structure determination (nitro ketone 1c ; Fig.). The nitro ketone 7 from cyclohex-2-enone and 4-methoxy-β-nitrostyrene was cyclized (via a silyl nitronate C ; Scheme 5) to the nitroso acetal 8 , and one of the bicyclic nitronate primary adducts 9 underwent a [3+2] cycloaddition to phenylacetylene and to ethyl 2-butynoate to give, after a ring-contracting rearrangement, tricyclic aziridine derivatives with five consecutive stereocenters ( 10 , 11 ; Scheme 5 and Table 2), in enantiomerically pure form. With an aliphatic nitro olefin, the Ti-TADDOLate-mediated reaction with (silyloxy)cyclohexene led to a moderate yield, but the product 4 was isolated in a high configurational purity.     

Synthesis of the Cyclopentyl Nucleoside (−)‐Neplanocin A from D‐Glucose via Zirconocene‐Mediated Ring Contraction

Two approaches for the conversion of d‐ glucose to (?) ‐neplanocin A ( 2 ), both based on the zirconocene‐promoted ring contraction of a vinyl‐substituted pyranoside, are herein evaluated (Scheme 1). In the first pathway (Scheme 2), the substrate possesses the α‐d‐ allo configuration (see 6 ) such that ultimate introduction of the nucleobase would require only an inversion of configuration. However, this precursor proved unresponsive to Cp₂Zr (=[ZrCl₂(Cp)₂]), an end result believed to be a consequence of substantive nonbonded steric effects operating in a key intermediate (Scheme 5). In contrast, the C(2) epimer (see 7 ) experienced the desired metal‐promoted conversion to an enantiomerically pure polyfunctional cyclopentane (see 5 in Scheme 3). The substituents in this product are arrayed in a manner such that conversion to the target nucleoside can be conveniently achieved by a double‐inversion sequence (Scheme 4). Recourse to palladium(0)‐catalyzed allylic alkylation did not provide an alternate means of generating 2 .     

Facile Preparation of (±)-12-Epiprostaglandins from 7-Oxabicyclo[2.2.1]hept-5-en-2-one via an all-cis-formyllactone related to Corey lactone

The bicyclic monoselenoacetal 7 , easily obtained from (±)-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 6 ) via a radical addition-acyl migration sequence, was converted to racemic 12-epiprostaglandins 3 and 4 . The key intermediate was the all-cis-formyllactone 2b related to Corey lactone (see 12 ; Scheme 1). The presence of a (tert-butyl)-dimethylsilyl protective group for the 11-OH substituent (prostaglandin numbering) was found to be crucial in avoidingβ -elimination and epimerization during the Wittig-Horner reaction (Scheme 2). Epimerization at C(12) at the formyllactone stage (see 2b ) was also possible and gave the known precursor 1b of naturally occurring prostaglandins and analogs.     

Synthesis of (2′S)‐2′‐Deoxy‐2′‐C‐methylpurine Nucleosides and Their Phosphoramidites

We describe the stereoselective synthesis of (2′S)‐2′‐deoxy‐2′‐C‐methyladenosine ( 12 ) and (2′S)‐2′‐deoxy‐2′‐C‐methylinosine ( 14 ) as well as their corresponding cyanoethyl phosphoramidites 16 and 19 from 6‐O‐(2,6‐dichlorophenyl)inosine as starting material. The methyl group at the 2′‐position was introduced via a Wittig reaction (→ 3 , Scheme 1) followed by a stereoselective oxidation with OsO₄ (→ 4 , Scheme 2). The primary‐alcohol moiety of 4 was tosylated (→ 5 ) and regioselectively reduced with NaBH₄ (→ 6 ). Subsequent reduction of the 2′‐alcohol moiety with Bu₃SnH yielded stereoselectively the corresponding (2′S)‐2′‐deoxy‐2′‐C‐methylnucleoside (→ 8a ).     

Nucleotides. Part LXXV

The reactivity of the 2′‐deoxy‐N⁴‐(phenoxycarbonyl)cytidine derivatives 3 and 4 with aromatic amines was studied to form new types of urea derivatives (see 5 – 10 ). On the same basis, labeling of 3 and 4 with 5‐aminofluorescein ( 14 ) was achieved to give the conjugates 15 and 17 , respectively (Scheme 1). Treatment of 17 with 2‐(4‐nitrophenyl)ethanol in a Mitsunobu reaction led to double protection of the fluorescein moiety (→ 18 ) and desilylation yielded 19 . Dimethoxytritylation (→ 20 ) and subsequent phosphitylations afforded the new building blocks 21 and 22 . Synthesis of the fully protected trimer 28 was achieved by condensation of 21 with 23 to 26 which after detritylation (→ 27 ) was coupled with 25 to give 28 (Scheme 2). Deprotection of all blocking groups was performed with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) in one step to give 29 . The synthesis of the decamer 5′‐d(C^FluCCG GCC CGC)‐3′ ( 33 ) started from 30 which was attached to the solid support and then elongated with 31, 32 , and 22 at the 5′‐terminal end (C^Flu=deprotected phosphate derivative of 22 ). Hybridization with the complementary oligomer 5′‐d(G GGC CGG GCG)‐3′ ( 34 ) showed the influence of the fluorescein label on the stability of the duplex.     

1,3-Dioxanone Derivatives from β-Hydroxy-carboxylic Acids and Pivalaldehyde. Versatile Building Blocks for Syntheses of Enantiomerically Pure Compounds. A Chiral Acetoacetic Acid Derivative Preliminary Communication

(R)-3-Hydroxybutyric acid (from the biopolymer PHB) and pivalaldehyde give the crystalline cis - or (R,R)-2-(tert-butyl)-6-methyl-1,3-dioxan-4-one ( 1a ), the enolate of which is stable at low temperature in THF solution and can be alkylated diastereoselectively ( →3, 4, 5 , and 7 ). Phenylselenation and subsequent elimination give an enantiomerically pure enol acetal 10 of aceto-acetic acid. Some reactions of 10 have been carried out, such as Michael addition (→ 11 ), alkylation on the CH₃ substituent (→ 13 ), hydrogenation of the C?C bond (→ 1a ) and photochemical cycloaddition (→ 16 ). The overall reactions are substitutions on the one stereogenic center of the starting β-hydroxy acid without racemization and without using a chiral auxiliary.     

Analogues of Sialic Acids as Potential Sialidase Inhibitors. Synthesis of C6 and C7 Analogues of N-Acetyl-6-amino-2,6-dideoxyneuraminic Acid

The piperidines 12 – 18 , piperidmose analogues of Neu5Ac ( 1 ) with a shortened side chain, were synthesized from N-acetyl-D -glucosamine via the azidoalkene 32 and tested as inhibitors of Vibrio cholerae sialidase. Deoxygenation at C(4) of the uronate 22 , obtained from the known D -GlcNAc derivative 20 , was effected by β-elimination (→ 23 ), exchange of the AcO at C(3) with a (t-Bu)Me₂SiO group and hydrogenation (→ 26 ; Scheme 1). Chain extension of 26 by reaction with Me₃SiCH₂MgCl gave the D -ido-dihydroxysilane 28 , which was transformed into the unsaturated L -xylo-mesylate 29 and further into the L -lyxo-alcohol 30 , the mesylate 31 , and the L -xylo-azide 32 . The derivatives 29 – 31 prefer a sickle zig-zag and 32 mainly an extended zig-zag conformation (Fig. 2). The piperidinecarboxylate 15 was obtained from 32 by ozonolysis (→ 33 ), intramolecular reductive animation (→ 34 ), and deprotection, while reductive animation of 34 with glycolaldehyde (→ 35 ) and deprotection gave 16 (Scheme 2). An intramolecular azide-olefin cycloaddition of 32 yielded exclusively the fused dihydrotriazole 36 , while the lactone 39 did not cyclize (Scheme 3). Treatment of 36 with AcOH (→ 37 ) followed by hydrolysis (→ 38 ) and deprotection led to the amino acid 18 . To prepare the (hydroxymethyl)piperidinecarboxylates 12 and 17 , 32 was first dihydroxylated (Scheme 4). The L -gluco-diol 40 was obtained as the major product, in agreement with Kishi's rule. Silylation of 40 (→ 42 ), oxidation with periodinane (→ 44 ), and reductive animation gave the L -gluco-piperidine 45 . It was, on the one hand, deprotected to the amino acid 12 and, on the other hand, N-phenylated (→ 46 ) and deprotected to 17 . While 45 and 12 adopt a ²C₅ conformation, the analogous N-Ph derivatives 46 and 17 adopt a ₅C² and a B_3,6 conformation, respectively, on account of the allylic 1,3-strain. The conformational effects of this 1,3-strain are also evident in the carbamate 47 , obtained from 45 (Scheme 5), and in the C(2)-epimerized bicyclic ether 48 , which was formed upon treatment of 47 with (diethylamino)sulfur trifluoride (DAST). Fluorination of 40 with DAST (→ 49 ) followed by treatment with AcOH led to the D -ido-fluorohydrin 50 . Oxidation of 50 (→ 51 ) followed by a Staudinger reaction and reduction with NaBH₃CN afforded the (fluoromethyl)piperidine 52 , while reductive amination of 51 with H₂/Pd led to the methylpiperidine 55 , which was similarly obtained from the keto tosylate 54 and from the dihydrotriazole 36 . Deprotection of 52 and 55 gave the amino acids 13 and 14 , respectively. The aniline 17 does not inhibit V. cholerae sialidase; the piperidines 12 – 16 and 18 are weak inhibitors, evidencing the importance of an intact 1,2,3-trihydroxypropyl side chain.     

1,2endo-Trimethylenenorbornane. A novel isomer of adamantane

An easy approach to the novel adamantane isomer 1,2endo-trimethylenenorbornane (2) is described. Starting from a mixture of pent-4-ynylcyclopentadienes 3 the tricyclic monosaturated key intermediate 5 was prepared by intramolecular cycloaddition (→ 4 ) and subsequent regioselective reduction of the C(5), C(6) double bond. The title hydrocarbon 2 was obtained from 5 upon stereoselective hydrogenation by diimide. In addition specifically deuteriated analogues of 2 were prepared applying dideuteriodiimide. Compound 2 rearranged to 2endo, 6endo-trimethylenenorbornane (4-homobrendane, 10 ) in sulfuric acid as well as with aluminium bromide in carbon disulfide.