The Deoxygenation and Isomerization of Artemisinin and Artemether and Their Relevance to Antimalarial Action

The treatment of artemisinin ( 1 ) and β-artemether ( 6 ) with Zn dissolving in AcOH for a few hours results in mono-deoxygenation giving deoxyartemisinin ( 5 ) and deoxy-β-artemether ( 7 ), respectively, as the sole product. In contrast, submission of 1 to FeCl₂ · 4 H₂O in MeCN at room temperature for 15 min causes only isomerization, (3aS,4R,6aS,7R,10S,10aR)-octahydro-4,7-dimethyl-8-oxo-2H-10H-furo[3,2-i] benzopyran-10-yl acetate ( 8 ) and (3R)-3-hydroxydeoxyartemisinin ( 9 ) being produced in 78 and 17% yield, respectively. The action of FeCl₂ · 4 H₂O in MeCN on 6 is similar. Under the same conditions, 6 gives products analogous to 8 and 9 accompanied by an epimeric mixture of 2-[4-methyl-2-oxo-3-(3-oxobutyl)cyclohexyl]propanaldehyde in yields of 32, 23, and 16%, respectively. No epoxide is formed on repeating the last two experiments in the presence of cyclohexene. The deoxygenation of 1 and 6 by Zn is rationalized in terms of its oxophilic nature. The catalyzed isomerization of 1 and 6 by Fe²⁺ is attributed to the redox properties of the Fe²⁺/Fe³⁺ system.     

Competing Fragmentation,Substitution and Elimination in the Solvolysis of Alkylated 3-Chloropropanols and their Ethers. Fragmentation reactions no. 28

The unstrained 3-chloroalcohols 1a , 2a and 3a do not undergo solvolytic fragmentation in neutral and weakly acidic 80% ethanol, only substitution and elimination products being formed by the limiting S_N1-E1 mechanisms. This also applies to the corresponding ethers 1b and 3b . Addition of sodium hydroxide causes the observed rate constants for the 3-chloroalcohols to rise steeply by factors of at least 10³ to 10⁵. These level off at higher base concentrations due to an opposing ionic strength effect. Whereas 3a fragments quantitatively in the presence of base, 1a and 2a fragment in competition with elimination to the Δ³-olefins 9a and 10 , respectively. 2a also yields 2% of the oxetane 6b . These results support a concerted base-induced fragmentation mechanism which competes with intramolecular base-induced elimination (E_i) in the case of the acyclic chloroalcohols 1a and 2a . The formation of small amounts of the oxetane 6b from 2a is attributed to intramolecular nucleophilic substitution at the tertiary carbon atom.     

Fused pyrimidines. 7. Nucleosides of pyrimidopyrimidinediones and pteridinediones as potential chemotherapeutic agents

Several nucleoside derivatives of pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione 1 and 2,4{1H,3H-pteridinedione 2 were prepared. Treating the appropriate silylated nucleobase with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofura-nose 3 in the presence of trimethylsilyl Inflate gave 4 and 8 which, upon debenzoylation, gave 5 and 9 , respectively. Treatment of 4 with phosphorus pentasulfide afforded the sulfur substituted compound 6 . Again, deprotection gave 7 . The arabinose derivatives were obtained by treating 1-O-acetyl-2,3,5-tri-O-benzoyl-D-arabinofuranose 10 with the silylated nucleobases to give 11 and 13 . Debenzoylation gave the free arabinonucleosides 12 and 14 respectively. The deoxy derivative 16 was prepared by the reaction of 1 with 1-chloro-3,5-di-O-acetyl-2-deoxy-D-ribofuranose 15 . Deacetylation of 16 with methanolic ammonia gave the α-anomer 17 .     

Research on photochemical and thermochemical reactions between indole and quinones in the absence of solvent

The solid state photochemical reaction of indole with 1,4-naphthoquinone yielded 5H-dinaphtho[2,3-a:-2′,3′-c]carbazole-6,11,12,17-tetrone ( 1 ) in addition to 2-(3-indolyl)-1,4-naphthoquinone ( 2 ) which was also the only product in the solution photoreaction. Solventless thermochemical reactions of indole with phenanthrenequinone in the presence or absence of zinc chloride gave 10-(1H-indol-3-yl)-9-phenanfhrenol ( 3 ) and 9,10-dihydro-9-(1H-indol-3-yl)-10-(3H-indol-3-ylidene)-9-phenanthrenol ( 4 ) or 10,10-di-1H-indol-3-yl-9(10H)-phenanthrenone ( 5 ), respectively. All of these products were only obtained in trace amount in corresponding solution reactions, and are different from the adduct 10-hydroxy-10-(1H-indol-3-yl)-9(10H)-phenanthrenone ( 6 ) obtained in the solution photoreaction. A possible mechanism for formation of 4 and 5 is described in terms of electron pair donor/acceptor complexation.     

Nucleosides and nucleotides. Solid-phase synthesis of oligonucleotides on an insoluble, macroporous carrier

Insoluble, macroreticular, highly cross-linked polystyrene with projecting mono-methoxytrityl chloride groups 4 was prepared and condensed with thymidine (TD ) as well as with 1-(2′-deoxy-ß-D-ribofuranosyl)-2(1H)-pyridone (II_d) to give the polymers 5 and 6 respectively, containing approximately 465 μmoles resp. 650 μmoles of bound nucleoside per gram of polymer. A standard procedure for removal of the products from the support is described. Condensation of the polymer-bound nucleosides 5 and 6 , respectively, with 3′-O-acetyl-thymidine-5′-phosphate ( 7 ) in the presence of mesitylenesulfonyl chloride (MS) and subsequent removal from the polymer yielded the dinucleoside phosphates T_d-T_d ( 9 ) and II_d-T_d ( 11 ) respectively. Condensation of the polymer 8 with 3′-O-acetyl-thymidine-5′-phosphate ( 7 ) in the presence of MS and cleavage of the polymer linkage gave the trithymidine diphosphate (T_d-T_d-T_d) ( 13 ). Phosphorylation of the polymer-bound nucleosides 5 and 6 with ß-cyanoethyl phosphate in presence of MS took place in 3′-position. Similarly the polymer-bound dinucleoside phosphates 8 and 10 gave 16 and 17 respectively.     

The chemistry of polycyclic arene imines. II. Photochemistry of phenanthrene 9,10-imine and of its N-butyl derivative

The uv irradiation of phenanthrene 9, 10-imine has been shown to give 9H-tetrabenzo[a, c, g, i]carbazole as the major photo-product both in argon purged acetone and in dichloromethane. Phenanthrazine, N-9-phenanthrenyl-9-phenanthrenamine and phenanthrene were formed in smaller quantities. 9-Phenanthrenamine was found to be a minor by-product. N-Butylphenanthrene 9, 10-imine yielded under similar conditions phenanthrene and N-butyl-9-phenanthrenamine as the only isolable polycyclic compounds. In the presence of air the substituted imine gave mainly 2-propylphenanthro[9, 10-d]oxazole.     

Regio‐ and Stereoselectivity in the Lewis Acid‐ and NaH‐Induced Reactions of Thiocamphor with (R)‐2‐Vinyloxirane

The reaction of the enolizable thioketone (1R,4R)‐thiocamphor (= (1R,4R)‐1,7,7‐trimethylbicyclo[2.2.1]heptane‐2‐thione; 1 ) with (R)‐2‐vinyloxirane ( 2 ) in the presence of a Lewis acid such as SnCl₄ or SiO₂ in anhydrous CH₂Cl₂ gave the spirocyclic 1,3‐oxathiolane 3 with the vinyl group at C(4′), as well as the isomeric enesulfanyl alcohol 4 . In the case of SnCl₄, an allylic alcohol 5 was obtained in low yield in addition to 3 and 4 (Scheme 2). Repetition of the reaction in the presence of ZnCl₂ yielded two diastereoisomeric 4‐vinyl‐1,3‐oxathiolanes 3 and 7 together with an alcohol 4 , and a ‘1 : 2 adduct’ 8 (Scheme 3). The reaction of 1 and 2 in the presence of NaH afforded regioselectively two enesulfanyl alcohols 4 and 9 , which, in CDCl₃, cyclized smoothly to give the corresponding spirocyclic 1,3‐oxathiolanes 3, 10 , and 11 , respectively (Scheme 4). In the presence of HCl, epimerization of 3 and 10 occurred to yield the corresponding epimers 7 and 11 , respectively (Scheme 5). The thio‐Claisen rearrangement of 4 in boiling mesitylene led to the allylic alcohol 12 , and the analogous [3,3]‐sigmatropic rearrangement of the intermediate xanthate 13 , which was formed by treatment of the allylic alcohol 9 with CS₂ and MeI under basic conditions, occurred already at room temperature to give the dithiocarbonate 14 (Schemes 6 and 7). The presented results show that the Lewis acid‐catalyzed as well as the NaH‐induced addition of (R)‐vinyloxirane ( 2 ) to the enolizable thiocamphor ( 1 ) proceeds stereoselectively via an S_N2‐type mechanism, but with different regioselectivity.     

Desoxy-nitrozucker 14. Mitteilung 1-C-Nitroglycale. Herstellung und Umsetzung mit einigen Stickstoff-Nucleophilen

1-C-Nitroglycals. Preparation and Reaction with Some Nitrogen Nucleophiles Acetylation of the 1-deoxy-1-nitromannopyranoses 2 and 6 was accompagnied by spontanous β-elimination to give the 1-C-nitroglucals 3 and 7 , respectively, while acetylation of the gluco- and galacto-configurated 1-deoxy-1-nitropyranoses 8 and 14 gave the acetates 9 and 15 , respectively (Scheme 1). The acetylation of the ribo- and arabino-configurated 1-deoxy-1-nitrofuranoses 19 and 21 also occurred without β-elimination to give the acetates 20 and 22 , respectively (Scheme 2). Mild base treatment of the previously described O-acetylnitro-β-D -glucose 4 , the O-acetylnitro-β-D -pyranoses 9 and 15 , and the O-acetylnitro-β-D -furanoses 17 , 20 , and 22 gave the 1-C-nitroglycals 3 , 10 , 16 , 18 and 23 , respectively (Scheme 1 and 2). The previously obtained 1-C-nitroglucal 3 was deacetylated by treatment with MeOH in the presence of KCN or sodium m-nitrophenolate to give the free nitroglucal 5 . Deacetylation of the benzylidene protected 1-C-nitroglucal 10 (MeOH, NaOMe) gave the 4,6-O-benzylidene-1-C-nitroglucal 11 and traces of the 2-O-methyl-1-C-nitromannoses 12 and 13 . The UV, IR, ¹H-NMR and ¹³C-NMR spectra of the 1-C-nitroglycals are discussed. In solution, the 1-C-nitroglycals 1 , 5 , 7 , 10 , 11 , and 16 adopt approximately a ⁴H_5? and 3 a flattened ⁴H₅ conformation. The structure of 5 was established by X-ray analysis. In the solid state, 5 adopts a sofa conformation, which is stabilized by an intramolecular H-bond. The β-addition of NH₃ to the 1-C-nitroglucals 7 and 10 was followed by an O→ N acetyl migration to give exclusively anomeric pairs of the N-acetyl-1-nitromannosamine derivatives 24 / 25 and 26/27 , respectively (Scheme 3). The β-addition of methylamine, octadecylamine, and tryptamine to the 1-C-nitroglucal 11 also stereoelectronically controlled and gave the crystalline N-alkyl-1-nitromannosamines 28 , 29 , and 30 , respectively. The stereoelectronically controlled β-addition of NH₃ to the 1-C-nitrogalactal 16 , followed by acetylation, yielded exclusively the talosamine derivative 31 , while the reversible β-addition of azide ions to 16 gave the anomeric 2-azido-1-nitrogalactoses 32 and 33 . The β-addition of azide ions to the 1-C-nitroglucal 1 led to the 2-azido-1-nitromannose 34 . In the presence of excess formaldehyde, this addition was followed by a Henry reaction. Chromatography of the crude product was accompagnied by solvolytic removal of the NO₂ group to give the 3-azidomannoheptulose 35 in high yields (Scheme 4).     

Regio‐ and Stereoselectivity of the SiO2‐Catalyzed Reaction of Thiocamphor (=1,7,7‐Trimethylbicyclo[2.2.1]heptane‐2‐thione) with Optically Active Monosubstituted Oxiranes

The reactions of the enolizable thioketone (1R,4R)‐thiocamphor (=(1R,4R)‐1,7,7‐trimethylbicyclo[2.2.1]heptane‐2‐thione; 1 ) with (S)‐2‐methyloxirane ( 2 ) in the presence of a Lewis acid such as SnCl₄ or SiO₂ in anhydrous CH₂Cl₂ led to two diastereoisomeric spirocyclic 1,3‐oxathiolanes 3 and 4 with the Me group at C(5′), as well as the isomeric β‐hydroxy thioether 5 (Scheme 2). The analogous reactions of 1 with (RS)‐, (R)‐, and (S)‐2‐phenyloxirane ( 7 ) yielded two isomeric spirocyclic 1,3‐oxathiolanes 8 and 9 with Ph at C(4′), an additional isomer 13 bearing the Ph group at C(5′), and three isomeric β‐hydroxy thioethers 10, 11 , and 12 (Scheme 4). In the presence of HCl, the β‐hydroxy thioethers 5, 10, 11 , and 12 isomerized to the corresponding 1,3‐oxathiolanes 3 and 4 (Scheme 3), and 8, 9 , and 13 , respectively (Scheme 5). Under similar conditions, an epimerization of 3, 8 , and 9 occurred to yield the corresponding diastereoisomers 4, 14 , and 15 , respectively (Schemes 3 and 6). The structures of 9 and 15 were confirmed by X‐ray crystallography (Figs. 1 and 2). These results show that the Lewis acid‐catalyzed addition of oxiranes to enolizable thioketones proceeds with high regio‐ and stereoselectivity via an S_n 2‐type mechanism.     

Amino acids in the synthesis of heterocyclic systems. Synthesis of γ-(5-(1,2,4-Triazinylidene))-α,β-dehydro-α-amino acid derivatives and 6H-pyrido[1,2-d][1,2,4]triazin-6-ones

5-(1,2,4-Triazinyl) substituted enamines 3 react with 5(4H)-oxazolones 4 in acetic anhydride to give acetylated products 5 , while in toluene-acetic acid mixture nonacetylated products 9 are formed. Both types of products were isolated as (E,Z) mixtures. Compounds 5 and 9 rearrange into 6H-pyrido[1,2-d]-[1,2,4]triazin-6-ones 12 by heating in formic acid or in xylene, respectively. Compounds 5 are transformed in the presence of nucleophiles, such as sodium alkoxides or sodium amides via anionic form 10 into corresponding esters 13 and amides 14 of γ-(5-(1,2,4-triazinylidene)) substituted derivatives of α-amino-2-butenoic acid, which exist in 2-(Z),4-(Z) form.     

The chemistry of arene imines. IV. An unusual silver promoted transformation of N-chlorophenanthrene 9,10-imine into 9,10-phenanthrenequinone dialkyl acetals

Methanolic silver nitrate and perchlorate convert N-chlorophenanthrene 9,10-imine (1) into 10,10-dimethoxy-9(10H)-phenanthrone (2) in 60% yield. Substitution of the mthanol by ethanol, 1- and 2-propanol gives phenanthrenequinone diethyl-, di-1-propyl- and di-2-propylacetals (3-5) , respectively. Silver acetate promotes these transformations only in the presence of a protic acid. The reaction mechanism is assumed to involve the generation of a cyclic nitrenium ion, nucleophilic ring opening by methanol, hydrolysis of the imine function and silver ion promoted oxidation.     

Dihydropyrimidines and related structures. I. N2-substituted 2-pyrimidinamines and dihydro-2-pyrimidinamines by reaction of phenylbutenones and monosubstituted guanidines

The reactions of monosubstituted guanidines 2 with phenylbutenones 7 and 10 exclusively yield N²-substituted 2-pyrimidinamines 8 and 9 . The structure of the reaction products is proved and their differing stability is discussed. Action of methyl- and benzylguanidine respectively ( 2b, c ) on 4-phenyl-3-buten-2-one ( 7 ) and of 2c on l-phenyl-2-buten-1-one ( 10 ) under atmospheric oxygen affords aromatic N²-substituted 2-pyrimidinamines 9b and c . The dihydropyrimidines 8b and c, probable intermediates of the reactions, could not be isolated. In contrast, heating of arylguanidines 2d , e with 7 leads to stable dihydropyrimidinarnines 8d and e, which can be isolated as bases. Addition of methanol to 8d yields 6-methoxy-2-pyrimidinamine 11d , boiling of 8d in DMF affords 9d . Under nitrogen, guanidine adds to 7 to yield aminopyrimidinol 13a , which is transformed by heating in benzene into pyrimidine 9a . The low stability of 8a-c is attributed to their strong basicity, the greater stability of 8d and e to their lower basicity. The structural formulae of 8d , e and 9b-d and their salts respectively were established partly ( 8e ) by nmr and partly ( 9b-d ) by comparison of the corresponding picrates with authentic samples [17].     

Natural product chemistry. Part 153 . Synthesis and possible anticancer activity of 8-nitronoracronycine

Since the strategy for the synthesis of 9-, 10- and 11-nitronoracronycine [3,4] could not be applied to the 8-nitronoracronycine 9 , we here report the preparation of the latter by a fusion of methyl 2-amino-6-nitrobenzoate 2 and phloroglucinol 3 . The fusion of 2 and 3 gave 1,3-dihydroxy-8-nitro-9(10H)-acridinone 6 . Subsequent methylation, demethylation and reaction with 2-chloro-2-methyl-3-butyne afforded the desired 8-nitronoracronycine 9 . Compound 9 , 1,3-dimethoxy-10-methyl-8-nitro-9(10H)-acridinone 7 and 1,3-dihydroxy-10-methyl-8-nitro-9(10H)-acridinone 8 were tested by the National Cancer Institute (NCI) for possible anticancer activity.     

Hetero-Diels-Alder cycloadditions of α,β-unsaturated acyl cyanides. Part 2. Reactions with N,N-dimethyluracils,a new route to 5-substituted uracil derivatives

The [4 + 2] cycloadditions of 2-oxobut-3-enenitrile ( 1a ), 2-oxopent-3-enenitrile ( 1b ), and ethyl 4-cyano-4-oxobut-2-enoate ( 1c ) with 1,3-dimethyluracil ( 2 ), 1,3, 6-trimethyluracil ( 9 ), or 1,3,5-trimethyluracil ( 16 ) were investigated. The reactions of 1a with 2 or with 9 lead to bicyclic adducts 3 and 10 , respectively. These hexahydro-cis-pyranopyrimidines undergo ring opening under acidic conditions, restoring in 4 and 11 , respectively, an uracil system comprising 2-hydroxybut-2-enenitrile as a side chain at C(5). The surprisingly stable enols tautomerize slowly to the corresponding acyl cyanides 6a and 13a , respectively. Reacting 1b or 1c with 2 and with 9 does not afford cycloadducts; instead the uracil derivatives 6b, c and 13b, c , respectively, show up, carrying at C(5) α-oxobutanenitrile side chains. Cleavage of the acyl cyanide functions in 6a–c and 13a–c with nucleophilic agents produces various acids, esters, or amides, i.e. derivatives 8a–c and 15–c , respectively. The methyl esters 8a (X ? MeO, R ? H) and 15a (X ? MeO, R ? H) are also formed directly from the adducts 3 and 10 , respectively, with acid or base catalysis in presence of MeOH. The cycloadducts 17a and 17c , resulting from the reaction of 1a and 1c with 16 , respectively, have a Me group at the ring junction C(4a) and are stable. The structure of 17c proves that this hetero-Diels-Alder addition of inverse electron demand follows the endo-mode.     

Pyrimidines. 65. Synthesis of 6-substituted thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones

Several 6-substituted thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives were synthesized. 6-Ethoxycarbonyl derivatives 3 and 7 were prepared by treatment of 6-chloro-5-formyluracil 1 and 6-chloro-5-cyanouracil 6 with ethyl 2-mercaptoacetate in the presence of a base. Electrophilic substitution reactions (Vilsmeier-Haack reaction, bromination, and nitration) of 5,6-unsubstituted thieno[2,3-d]pyrimidine 9 , prepared by condensation of 6-mercaptouracil 8 with chloroacetaldehyde, afforded the corresponding 6-formyl-, 6-bromo-, and 6-nitrothieno[2,3-d]pyrimidines 10, 15 and 16 , respectively.     

Photocycloaddition of Isocoumarins and Isothiocoumarins to Alkenes

On irradiation in the presence of tetrachloroethene (TCE), both isocoumarins 3 and isothiocoumarins 4 afford in high yields the cis‐fused cycloadducts 8 and 9 , while only the oxacycles 3 undergo photocycloaddition to 2,3‐dimethylbut‐2‐ene (TME) to give mixtures of cis‐ and trans‐fused products 10 and 11 , respectively, in moderate yields. This higher efficiency in reacting with TCE as compared to TME for compounds 3 and 4 contrasts the behavior of simple cyclic enones, e.g., 5,5‐dimethylcyclohex‐2‐enone ( 12 ), which is converted to bicyclooctanones about fifty times faster with TME than with TCE.     

High Acceleration and Improved Diastereoselectivity of Intramolecular Ene-Type Reactions by Diethylaluminum Chloride. Preliminary Communication

The pyrrolidines 2 and 10 were obtained by thermal ene-reactions at +70° and +180° from the (Z)-4-aza-1, 6-diene 1 and from the (E)-4-aza-1, 6-diene 9 in the ratios of 75:25 and 50:50, respectively. On the other hand, these cyclizations proceeded readily in the presence of diethylaluminum chloride at ? 78° and ? 35° giving in high yield the trans-pyrrolidine 2 from 1 with 100% and from 9 with 89% diastereoselectivity.     

Furopyridines. VI. Preparation and reactions of 2- and 3-substituted furo[2,3-b]pyridines

This paper describes the synthesis and chemical properties of some 2- and 3-substituted furo[2,3-b]pyridines. Reaction of ethyl 2-chloronicotinate 1 with sodium ethoxycarbonylmethoxide or 1-ethoxycarbonyl-1-ethoxide gave β-keto ester 2 or ketone 5 , respectively. Ketonic hydrolysis of 2 afforded ketone 3, from which furo[2,3-b]pyridine 4 was obtained by the method of Sliwa. While, 2-methyl derivative 7 was prepared from 5 by reduction, O-acetylation and the subsequent pyrolysis. Reaction of ketone 3 with methyllithium gave tertiary alcohol 8 which was O-acetylated and pyrolyzed to give 3-methyl derivative 9 . Formylation of 4 , via lithio intermediate, with DMF yielded 2-formyl derivative 10 , from which 7 , was obtained by Wolff-Kishner reduction. Dehydration of the oxime 11 of 10 gave 2-cyano derivative 12 , which was hydrolyzed to give 2-carboxylic acid 13 . Reaction of 3-bromo compound 14 with copper(I) cyanide gave 3-cyano derivative 15 . Alkaline hydrolysis of 15 afforded compound 16 and 17 , while acidic hydrolysis gave carboxamide 18 . Reduction of 15 with DIBAL-H afforded 3-formyl derivative 19 . Wolff-Kishner reduction of 19 gave no reduction product 9 but hydrazone 20 . Reduction of tosylhydrazone 21 with sodium borohydride in methanol afforded 3-methoxymethylfuro[2,3-b]pyridine 22 .     

N-bis(methylthio)methylene derivatives. 5. New synthesis of 2-aminoindolizine and related compounds via a formal [3 + 3] cycloaddition reaction using N-bis(ethoxycarbonylmethylthio)methylenephenylsulfonamides

Reaction of pyridinium N-ylide 5a with N-bis(ethoxycarbonyl)methylthio)(p-substituted-phenyl)sulfon-amides 2a,c in the presence of triethylamine as a base in ethanol gave diethyl 2-(p-substituted-phenylsulfonyl)aminoindolizine-1,3-dicarboxylates 9a,b via a new formal [3 + 3] cycloaddition reaction. In a similar manner, 2-sulfonylaminopyrrolo[2,1-a]isoquinoline derivatives 11a-e were also obtained by the reaction of 2a-c and 4a,b with the corresponding isoquinoline N-ylides 10a.b with good results.     

Glycosylidene Carbenes. Part 4. Synthesis of Spirocyclopropanes from Acetamidoglycosylidene-Derived Diazirines

The synthesis of the first glycosylidene-derived 2-acetamido-2-deoxydiazirine 4 from N-acetylglucosamine 6 is described. Thus, 6 was transformed into the 3-O-mesylglucopyranoside 9 by glycosidation with allyl alcohol, benzylidenation, and mesylation (Scheme 2). Solvolysis of 9 gave the allopyranoside 10 which, upon benzylation and glycoside cleavage, yielded the hemiacetals 12 . Using our established method (via the lactone oxime 14 and the diaziridines 16 ), 12 gave the diazirine 4 . Thermolysis of this diazirine in the presence of i-PrOH gave the dihydro-1,3-oxazole 5 (Scheme 1); in the presence of acrylonitrile, the four diastereoisomeric spirocyclopropanes 17–20 and the acetamidoallal 21 were obtained and separated by prep. HPLC (Scheme 3). Assignment of the configuration of 17–20 is based on NOE measurements and on the effect of diamagnetic anisotropy of the CN group. The ratio of the four cyclopropanes, which is in keeping with earlier results, is rationalized.