Heterodiamantane und strukturell verwandte Verbindungen. III.. Pentacyclische diäther der C11-reihe. 5, 13-Dioxapentacyclo-[6.5.0.02,6.03,12.04,9]tridecan, 4, 13-dioxapentacyclo [6.4.1.02,7.03,10.05,9]tridecan und 3, 10-dioxapentacyclo [7.3.1.02,7.04,12.06,11]tridecan

Heterodiamantanes and Structurally Related Compounds. Part III. The Pentacyclic C₁₁-Diethers 5, 13-Dioxapentacyclo [6.5.0.0^2,6.0^3,12.0^4,9]tridecane, 4, 13-Dioxapentacyclo [6.4.1.0^2,7.0^3,10.0^5,9]tridecane, and 3, 10-Dioxapentacyclo [7.3.1.0^2,7.0^4,12.0^6,11]tridecane In connection with the studies on heterodiamantanes and structurally related compounds the three novel pentacyclic diethers 3 – 5 were prepared starting from the cyclopentadienone dimer 6 . All four compounds have as common features a central carbocyclic 6-membered ring with four axial alkyl substituents and two oxygen functions in 1, 4 position. The required eleventh C-atom was introduced by dichlorocarbene addition either to 6 ( → 7 ) (Scheme 2) or to 29 ( → 28 ) (Scheme 4). Diether 3 was obtained by reduction of 26 (Scheme 2), a suitable precursor prepared either by intramolecular addition ( 24 → 26 ; Scheme 2) or substitution ( 30 → 26 , 31 → 26 ; Scheme 4), as well as by direct substitution ( 44 → 3 , 42 → 3 ; Scheme 5). Diether 4 was the product of a direct substitution ( 39 → 4 , 36 → 4 ; Scheme 5). The synthesis of diether 5 was achieved from the addition product 51 (resulting from the alcohols 47 and 48 ; Scheme 6). Diether 4 is the thermodynamically least stable of the three diethers 3 – 5 . It was easily isomerized to 5 on treatment with concentrated sulfuric acid in benzene whereas 3 and 5 remained unchanged under these conditions.     

Photochemische Reaktionen. 109. Mitteilung [1]. Zur Photochemie konjugierter δ-Keto-enone und β,γ,δ,ϵ-ungesättigter Ketone

Photochemistry of Conjugated δ-Keto-enones and β,γ,δ,?-Unsaturated Ketones On ¹π,π*-excitation the δ-keto-enones 5–8 are isomerized to compounds B ( 18 , 22 , 26 , 28 ) via 1,3-acyl shift and to compounds C ( 19 , 23 , 27 , 29 ) via 1,2-acyl shift, whereas the β,γ,δ,?-unsaturated ketone 9 gives the isomers 32 and 33 by 1,2-and 1,5-acyl shift, respectively. Furthermore, isomerization of 6 to 24 , dimerization of 8 to 30 and addition of methanol to 8 ( 8 → 31 ) is observed. Unlike 7 and 8 the acyclic ketones 5 , 6 and 9 undergo photodecarbonylation on ¹π,π*-excitation ( 5 → 20 , 21 ; 6 → 20 , 25 ; (E)- 9 → 35–38 ). Evidence is given, that the conversion to B as well as the photodecarbonylation of 5,6 and 9 arise from an excited singulet state, but the conversion to C as well as the dimerization of 8 from the T₁-state.     

A (1→4)-β-D-Glucuronan Excreted by a Mutant of the Rhizobium Meliloti M5N1 Strain

Abstract

A mutant of the R. meliloti M5N1 strain has been selected. This strain, R. meliloti M5N1 CS (NCIMB 40472), excretes an extracellular material composed of 2-O-Ac-β-GlcpA, 3-O-Ac-β-GlcpA, 2,3-di-O-Ac-β-GlcpA and three species of β-GlcpA residues 1→4 linked. For the culture conditions used, the weight average molecular weight of the polymer varied in the range of 6 × 10⁴ < Mw < 4 × 10⁵. High molecular weight glucuronate forms thermoreversible gels at 5 g L^?l. In the presence of divalent cation such as Ca²⁺ or trivalent cations such as Cr³⁺ or Fe^{3 +}, cross linking of the polymer occurs. This polysaccharide is the first exocellular (1→4)-β-D-glucuronan produced by a R. meliloti strain.     

Photochemische Reaktionen. 97 Mitteilung [1]. Zur Photochemie konjugierter Epoxy-diene II. Versuche mit (E)-β-Jonyliden-epoxiden

Photolysis of Conjugated Epoxy-dienes Direct and sensitized excitation of the (E)-β-ionylidene-epoxides 1 and 4 leads to different types of isomerizations. Thus photocycloelimination to the cyclopropene-ketones 2 and 6 is only achieved by ¹(π, π*)-excitation (λ=254 nm), whereas ³(π, π*)-excitation (λ > 280 nm, acetone) gives selective C(1′), O-cleavage of the oxirane ( 1 → 7 – 10 and 4 → 11 – 13 ). In contrast to 1 the twofold methylsubstituted epoxy-diene 4 shows mainly (E/Z)-isomerization ( 4 → 5 ) on both ¹(π, π*)- and ³(π, π*)-excitation while the isomerizations 4 → 6 and 4 → 11 – 13 are minor processes, only.     

Ring transformations of heterocycles. Part 1. Transformation of 4-amino-Δ2-1,2,4-oxadiazolines into 1,3,4-oxadiazoles

3-Aryl-4-amino-δ²-1,2,4-oxadiazolines 3 and their N-chloroacetyl derivatives 4 , upon treatment with chloroacetic anhydride in refluxing toluene, afford 2-chloromethyl-5-aryl-1,3,4-oxadiazoles 5 , suggesting the conversion sequence 3 → 4 → 5 . The generality of the new ring transformation 4 → 5 is supported similar conversion of other 4-(acylamino)-1,2,4-oxadiazolines 8 to 1,3,4-oxadiazoles 9 .     

Structural characterisation of a water-soluble polysaccharide from tissue-cultured Dendrobium huoshanense C.Z. Tang et S.J. Cheng

A water-soluble polysaccharide TC-DHPA4 with a molecular weight of 8.0 × 10⁵ Da was isolated from tissue-cultured Dendrobium huoshanense by anion exchange and gel permeation chromatography. Monosaccharide analysis revealed that the homogeneous polysaccharide was made up of rhamnose, arabinose, mannose, glucose, galactose and glucuronic acid with a molar ratio of 1.28:1:1.67:4.71:10.43:1.42. The sugar residue sequence analysis based on the GC-MS files and NMR spectra indicated that the backbone of TC-DHPA4 consisted of the repeated units:→6)-β-Galp-(1→6)-β-Galp-(1→4)-β-GlcpA-(1→6)-β-Glcp-(1→6)-β-Glcp-(→. The sugar residue sequences β-Glcp-(1→)-α-Rhap-(1→3)-β-Galp-(1→, β-Glcp-(1→4)-α-Rhap-(1→3)-β-Galp-(1→, β-Galp-(1→6)-β-Manp-(1→3)-β-Galp-(1→, and α-l-Araf-(1→2)-β-Manp-(1→3)-β-Galp-(1→ were identified as the branches attached to the C-3 position of (1→6)-linked galactose in the backbone.     

Stereoselective Synthesis of a Tetrameric Fragment of Streptococcus Pneumoniae Type 1 Containing an α-Linked 2-Acetamido-4-amino-2,4,6-trideoxy-D-galactopyranose (SUGp) Unit

Abstract

Block condensation of fully protected donor ethyl 1,2,3,4-tetra-O-benzyl-D-Rib-(5→P→6)-2,3,4-tri-O-benzoyl-l-thio-β-D-Glcp (2), having a (5→6)-phosphotriester union between the ribitol and the glucopyranosyl moieties, with the free 3′-OH group in the acceptor methyl 2-acetamido-4-O-(2-acetamido-4-(benzyloxycarbonyl)amino-2,4,6-trideoxy-α-D-Galp)-3,6-di-O-benzyl-2-deoxy-α-D-Galp (3), under the agency of N-iodosuccinimide and triflic acid, gave the fully protected tetrameric fragment 22. Elimination of the 2-cyanoethyl group from the phosphotriester and subsequent debenzoylation, followed by hydrogenolysis of the benzyl and benzyloxycarbonyl groups provided the target tetramer methyl D-Rib-(5→P→6)-D-Glcp-β(1→3)-Sugp-α(1→4)-α-D-GalpNAc (1).     

Stereoelectronic interactions: A booster for 4JHF transmission

Long-range proton-fluorine coupling constants (ⁿJ_HF) are helpful for the structure elucidation of fluorinated molecules. However, their magnitude and sign can change with the relative position of coupled nuclei and the presence of substituents. Here, trans-4-tert-butyl-2-fluorocyclohexanone was used as a model compound for the study of the transmission of ⁴J_HF. In this compound, the ⁴J_H6axF was measured to be +5.1 Hz, which is five times larger than the remaining ⁴J_HF in the same molecule (⁴J_H4F = +1.0 Hz and ⁴J_H6eqF = +1.0 Hz). Through a combination of experimental data, natural bond orbital (NBO) and natural J-coupling (NJC) analyses, we observed that stereoelectronic interactions involving the π system of the carbonyl group are involved in the transmission pathway for the ⁴J_H6axF. Interactions containing the π system as an electron acceptor (e.g., σ_{C6 H6ax} → π^*_C═O and σ_{C F} → π^*_C═O) increase the value of the ⁴J_H6axF, while the interaction of the π system as an electron donor (e.g., π_C═O → σ^*_{C F}) decreases it. Additionally, the carbonyl group was shown not to be part of the transmission pathway of the diequatorial ⁴J_H6eqF coupling in cis-4-tert-butyl-2-fluorocyclohexanone, revealing that there is a crucial symmetry requirement that must be fulfilled for the π system to influence the value of the ⁴J_HF in these systems.     

Reductive Radical Cyclisations of Bromo Acetals and (Bromomethyl)silyl Ethers of Terpenoid Alcohols

The tin hydride promoted and the reductive vitamin B₁₂ catalysed radical cyclisation of mixed 2-bromo-acetaldehyde acetals and of (2-bromomethyl)dimethylsilyl ethers of allylic terpenoid alcohols has been investigated: 3-oxadeca-5,9-dien-l-yl radicals undergo 5-‘exo’ cyclisation to oxolanes (Scheme 4), 3-oxa-2-siladeca-5,9-dien-1-yl radicals sequential 6-‘endo’→5-‘exo’ tandem cyclisation to cis-3-oxa-4-silabicyclo[4.3.0]nonanes (Scheme 5), and 3-oxa-2-silatetradeca-5,9,13-trien-l-yl radicals sequential 6-‘endo’→6-‘endo’→5-‘exo’ triple cyclisation to trans-transoid-trans- 12-oxa-11-silatricyclo[7.4.0.0^2,6] tridecanes (Scheme 6).     

Synthesis of Lacto‐ and Neolacto‐series Ganglioside Analogs Containing N‐Glycolylneuraminic Acid: Probes for Investigation of Specific Receptor Structures Recognized by Influenza A Viruses

Sialic acids are essential components of host‐cell surface receptors for infection of influenza virus. To investigate the specific receptor structures recognized by various influenza A viruses, a series of lacto‐ and neolacto‐series ganglioside analogs containing N‐glycolylneuraminic acid (Neu5Gc) have been synthesized. The pentasaccharide structures of Neu5Gc‐α‐(2→3)/(2→6)‐lactotetraose (IV³⁽⁶⁾Neu5GcLcOse) and Neu5Gc‐α‐(2→3)/(2→6)‐neolactotetraose (IV³⁽⁶⁾Neu5GcnLcOse) were constructed by glycosylation of the suitably protected trisaccharide acceptors (2A and 2B) with the Neu5Gc‐α‐(2→3)/(2→6)‐Gal trichloroacetimidate donors (1 and 21), respectively. Transformation of the 2‐(trimethylsilyl)ethyl group at the reducing end in 4, 11, 23, and 30 into the trichloroacetimidate group gave a series of Neu5Gc‐α‐(2→3)/(2→6)‐lacto‐ and neolactotetraose donors (7, 13, 26, and 33), which were coupled with 2‐(tetradecyl)hexadecanol (8), to give the corresponding glycolipids (9, 14, 27, and 34). Finally, the complete removal of the O‐acyl groups and saponification of the methyl ester group gave the desired ganglioside analogs (10, 15, 28, and 35).     

Fluoridhaltige Gäste in Alumosilicaten: Tetrafluoroborate in dem Sodalithen Na8Al6Si6O24(BF4)2

In the course of investigations on optical properties resulting from the interaction of fluorides with alumosilicate host materials and rare earth guests, a well defined BF₄^– ion wasfound to be incorporated within the sodalite of composition Na₈Al₆Si₆O₂₄(BF₄)₂. The resulting cubic molecular structure, which was determined by Rietveld methods (space group P4 n, a = 906.91 pm, wRp = 0.045, Rp = 0.027), contains one anion in each sodalite cage and is, contrarily to expectations, thermally stable. NMR spectroscopic investigations indicated a fast rotatory motion of the BF₄^– tetrahedra at room temperature and agreed with the tetrahedral BF₄^– ions found in IR and Raman spectra. Preliminary attempts to obtain a luminescent material by incorporation of Eu³⁺ through aqueous ion exchange only yielded low rare earth concentrations, giving rise to characteristic red emission lines at 581 nm (⁵D₀ → ⁷F₁) and 615 nm (⁵D₀ → ⁷F₂) in a 1:2 intensity ratio. The material unexpectedly exhibited a strong broad band emission at 520 nm after calcination under Ar, which is attributed to the formation of an Eu²⁺ species. Further calcination under air partially reestablished the Eu³⁺ emission.     

Isolierung und Strukturaufklärung von Neapolitanose (O-β-D-Glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→6)]-(D-glucose), einem neuen Trisaccharid aus den Stempeln von Gartenkrokussen (Crocus neapolitanus var.)

Isolation and Structure Elucidation of Neapolitanose (O-β-D -Glucopyranosyl-(1→2)-O-[β-D -glucopyranosyl-(1→6)]-D -glucose), New Trisaccharide from the Stigmas of Garden Crocusses (Crocus neapolitanus var.) From the stigmas of Crocus neapolitanus var. ‘Blue Bird’ two new crocetin glycosyl esters were isolated. They contained a hitherto unknown trisaccharide. For the structure elucidation a homonuclear 2D-¹H-NMR-shift-correlation experiment was carried out with the peracetate of the isolated trisaccharide. This experiment revealed that the carbohydrate is O-β-D -glucopyranosyl-(1→2)-O-[β-D -glucopyranosyl-(1→6))]-D -glucose, for which we suggest the name ‘neapolitanose’. The two new C₂₀-carotenoids from Crocus neapolitanus are crocetin (β-gentiobiosyl) (β-neapolitanosyl) ester ( 4 ) and crocetin di(β-neapolitanosyl) ester ( 5 ).     

Photochemische Reaktionen. 50. Mitteilung [1]. Zur Photochemie von gesättigten β-Ketosulfiden II. Synthese von 6-Hydroxy-2-thia-7-oxa-isotwistan

The results of the ultraviolet irradiation of the saturated β-ketosulfide 2 are discussed. The photochemistry of 2 is characterized by the occurrence of two primary photoprocesses. Their efficiences depend markedly on the excited transition, (charge-transfer)- or (n → π*)-excitation, respectively. In methanol solution (charge-transfer)-excitation leads almost exclusively to product 7 , due to (C_α – S)-fission, and (n → π*)-excitation to nearly equal amounts of 7 and of products 4 and 6 which result from α-cleavage. On solvent sensibilization in benzene products 4, 6, 7 and the still unidentified product 5 ² are formed. Compounds 4 and 6 have been described earlier [2]. The structure elucidation of 7 is reported in this paper. Acid-induced transformation of 7 yields the dihetero-isotwistane 15 .     

Photochemische Reaktionen. 116. Mitteilung [1]. Notiz zur 1γ, δ*-induzierten Photospaltung von γ, δ-Epoxy-eucarvon

π, π*-Induced Photocleavage of γ, δ-Epoxy-eucarvone . On ¹π, π*-excitation 1 undergoes cleavage of the C, C-oxirane bond ( 1 → c ) and isomerizes to the bicyclic dihydrofurane compound 5 . In addition, 1 shows photocleavage of the C (γ), O-oxirane bond ( 1 → d ) and gives the isomers 2, 3, 6, 7 and 8. Furthermore, the cyclohexenone 9 and the cyclohexene-1, 4-dione 10 are formed presumably via an intermediate 13 , which could also arise from d. Besides these products the compounds 11 and 12 are obtained, which are photoproducts of 2 .     

SYNTHESIS AND CATIONIC RING-OPENING POLYMERIZATION OF 1, 4-ANHYDRO-2, 3-DI-O-(P-AZIDOBENZYL)-α-D-RIBOPYRANOSE

New highly stereoregular 2, 3 -di- O-(p-azidobenzyl )-(1 →5 ) - α-D -ribofuranan was synthesized byselective ring-opening polymerization of 1, 4-anhydro-2, 3 - di-O -(p-azidobenzyl )-α-D -ribopyranose(ADABR) using phosphorus pentafluoride or tin tetrachloride as catalyst at low temperature indichloromethane. The monomer was obtained by the reaction of p - bromomethyl -phenyleneazide with 1, 4 -anhydro-α-D-ribose in DMF. The structure of poly(ADANR) was identified by specific rotation and ~(13)C-NMR spectroscopy. Acid chloride-AgCl_4 complex catalyst such as CH_2=C(CH_3)C~+OClO_4~- used in thepolymerization resulted in polymers with mixed structures, i.e. (1→5)-α-D-ribofuranosidic and (1→4)-β-D-ribopyranosidic units. However, with C_6H_5C~+OClO_4~- as catalyst, pure (1→5)-α-D-ribofuranan was obtained.The effects of catalyst, polymerization temperature and time on polymer stereoregularity were examined, andthe mechanism of the ring-opening polymerization was discussed.     

Two new complex triterpenoid saponins from Gledistsia dolavayi Franch.

Two new triterpenoid saponins, gledistside A ( 1 ) and gledistside B ( 2 ), isolated from the fruits of Gledistsia dolavayi Franch., were characterized as the 3,28‐O‐bisdesmoside of echinocystic acid acylated with monoterpene carboxylic acids. On the basis of spectroscopic and chemical evidence, their structures were elucidated as 3‐O‐β‐D ‐xylopyranosyl‐(1→2)‐α‐L ‐arabinopyranosyl‐(1→6)‐β‐D ‐glucopyranosyl‐28‐O‐β‐D ‐xylopyranosyl‐(1→3)‐β‐D ‐xylopyranosyl‐(1→4)‐[β‐D ‐galactopyranosyl‐(1→2)]‐α‐L ‐rhamnopyranosyl‐(1→2)‐{6‐O‐[2,6‐dimethyl‐6(S)‐hydroxy‐2‐trans‐2,7‐octadienoyl]}‐β‐D ‐glucopyranosylechinocystic acid ( 1 ) and 3‐O‐β‐D ‐xylopyranosyl‐(1→2)‐α‐L ‐arabinopyranosyl‐(1→6)‐β‐D ‐glucopyranosyl‐28‐O‐β‐D ‐xylopyranosyl‐(1→3)‐β‐D ‐xylopyranosyl‐(1→4)‐[β‐D ‐galactopyranosyl‐(1→2)]‐α‐L ‐rhamnopyranosyl‐(1→2)‐{6‐O‐[2‐hydroxymethyl‐6‐methyl‐6(S)‐hydroxy‐2‐trans‐2,7‐octadienoyl]}‐β‐D ‐glucopyranosylechinocystic acid ( 2 ). The complete ¹H and ¹³C assignments of saponins 1 and 2 were achieved on the basis of 2D NMR spectra including HMQC‐TOCSY, TOCSY, ¹H–¹H COSY, HMBC, ROESY and HMQC spectra. Copyright © 2002 John Wiley & Sons, Ltd.     

α-D-Glycosyl-Substituted α,α-D-Trehaloses with (1 → 4)-Linkage: Syntheses and NMR Investigations

Two symmetrical trehalose glycosyl ‘acceptors’ 4 and 6 were prepared and three of the unsymmetrical type, 8 , 10 , and 11 . Glucosylation of symmetrical ‘acceptor’ 4 gave a higher yield of trisaccharide (44%) than protect ve-group manipulation, namely via selective debenzylidenation 2 → 9 or monoacetylation 2 → 5 which proceeded in moderate yields (33–34%). A comparison of catalysts in the cis-glucosylation of trehalose ‘acceptor’ 10 with tetra-O-benzyl-β-D -glucopyranosyl fluoride 13 profiled triflic anhydride ((Tf)₂O) as a new reactive promoter yielding 92% of trisaccharide 14 , deblocking gave the target saccharide α-D -glucopyranosyI-( 1 → 4 )-α,α-D -trehalose. ¹H-NMR spectra of most compounds were analyzed extensively. The use of the ID TOCSY technique is advocated for its time efficiency, if needed supplemented by ROESY experiments.     

Doppelt und dreifach funktionalisierte,enantiomerenreine C4-Synthesebausteine aus β-Hydroxybuttersäure, Äpfelsäure und Weinsäure

Enantiomerically Pure Synthetic Building Blocks with Four C-Atoms and Two or Three Functional Groups from β-Hydroxy-butanoic, Malic, and Tartaric Acid The pool of chiral, non-racemic electrophilic building blocks, which are available from simple natural products in both enantiomeric forms is enlarged by the epoxides 3, 5 , and 10 , by the tosylate 12a , and by the aldehydes 18 (cf. symbols A-D , 14 , and Scheme 1). Key steps of the conversions leading from hydroxyacids to the building blocks are: epoxide-opening by triethylborohydride ( 1 → 2a ) and tosylate reduction ( 12a → 12b ); the Mitsunobu inversion ( 2a → 4a ); the reduction of (R, R)-tartaric ester to (R)-malic ester by NBS (N-bromosuccinimide) opening of the benzaldehyde acetal 8 and tin hydride reduction ( 6c → 7c ); the enantiomer enrichment of optically active ethyl β-hydroxy-butanoate through the crystalline dinitrobenzoate 21b . Detailed procedures are given for large scale preparations of the key intermediates. The enantiomeric purities of the building blocks are secured by correlations.     

Selectin Receptors 4: Synthesis of Tetrasaccharides Sialyl Lewis A and Sialyl Lewis X Containing A Spacer Group1,2

ABSTRACT

Synthesis of two isomeric tetrasaccharides, namely Neu5Acα(2→3)Galβ(1→3)[Fucα(1→4)GlcNAcβ (sLe^a) and Neu5Acα(2→3)Galβ(1→4)[Fucα(1→3)]GlcNAcβ (sLe^x) as 3-aminopropyl glycosides is described. Preparation of these compounds was performed by sialylation of selectively protected trisaccharides Le^a and Le^x which contain three unsubstituted OH groups at positions 2, 3 and 4 of Gal residue. Glycosylation of Le^x trisaccharide with ethylthio sialoside under promotion by NIS and TfOH in acetonitrile was effective and regio- and stereoselective to give sLe^x derivative in 81% yield. In contrast, sialylation of the Lc^a acceptor was accompanied by a variety of undesirable by-processes, namely. N-thioethylation of the GlcNAc residue, β-sialylation, and lactonisation. In order to improve the yield of sLc^a tetrasaccharide the glycosylation of Le^a acceptor by sialyl donors of ethyl and phenyl thioglycoside (promoted by NIS-TfOH or NBS-Bu₄NBr), xanthate (promotion by NIS-TfOH mixture or MeOTf) and phosphite (promoted by TMSOTf) types was also studied. Among the reactions investigated the glycosylation by phenyl thioglycoside sialoside promoted by NIS-TfOH gives the best yield (39%) of sLe^a tetrasaccharide product.     

Zum stereochemischen Verlauf der Biosynthese von 2-Oxo-pantolacton: Synthese von stereospezifisch indiziertem Pantolacton aus Äpfelsäure

(+)-Pantolactone¹ ( 13 ) has been synthesized from (?)-(S)-dimethyl malate (7) in 40% yield in a short sequence involving double alkylation (7 → 10 → 11 ), selective hydrolysis ( 11 → 12 ) and subsequent reduction ( 12 → 13 ). Through variation of the alkylating agents and preparation of the two diastereomeric 3-ethyl-3-methyl malates 14 and 15 it was possible to show that the diastereoselectivity of the second alkylation step is brought about by preferential attack from the Re-face of the critical enolate (9, see also Scheme 1). This knowledge, in turn, has been exploited for the synthesis of a sample of pantolactone specifically enriched with ¹³C in its Si-methyl group. Analysis of the ¹³C-NMR. spectrum of this sample together with the results of biosynthetic experiments previously reported by Aberhart demonstrates that the biological hydroxymethylation of 2-oxoisovaleric acid ( 3 ) to 2-oxopantoic acid ( 4 ), an important step in the biosynthesis of pantothenic acid, takes place in a retention mode (of. Scheme 2).