Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• galvanostatic conditions at a platinum electrode in DMF containing 6% water with NaBr as a supporting electrolyte. A mixture of products was formed, among them “3,5,6-trihydroxycholesterol” (probably cholesta-3β,5ξ,6ξ-triol), 7-oxocholesterol (9), 5,6-epoxycholesterol (10), and 7-ketocholesterol were identified

• electrochemical process. However, in some cases, reasonable yields of products are obtained and these reaction conditions may be of interest in practice. Preferential sites of cholesterol electrooxidation. Functionalization of the cholesterol side chain. Oxidation of cholestane-3β,5α,6β-triol triacetate (3) with

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• . The O-benzylated compound 14, however, proved to be more useful in the subsequent synthetic sequence. Thus, HCl-mediated deprotection of the acetal unit in 14 resulted in simultaneous removal of the silyl protecting group leading to the triol derivative 16 in an impressive yield of 89%. One-pot

• (95% yield, Scheme 3). Repetition of the synthetic sequence on 19 detailed for the conversion 13→18, i.e., protection of the diol as its dibenzylic ether 20, acid-mediated one-pot deprotection of the acetal and silyl moieties leading to the triol 21, redox manipulation of the vicinal diol unit in the

• latter to a hydroxymethyl unit, and subsequent debenzylation of the resulting 22 led to the desired tetrahydroxyquinolizidine derivative 23 in an overall yield of 45% over six steps. Similarly, the pentahydroxylated quinolizidine derivative 24 was prepared from the triol 21 in view of the importance of

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• [26] and threo-10 [27] were prepared from divinylcarbinol using asymmetric epoxidation [28][29]. Diastereomeric mixtures of 3-O-benzyl 11, 3-O-silyl-protected 12 and fully unprotected triol 13 was prepared starting from 1,2-O-isopropylidene-D-glyceraldehyde using described procedures [30]. The

• olefination using diethyl carbethoxyethylidenephopsphonate. Reduction of the resultant ester with DIBAL-H in dichloromethane afforded partially protected triol 36 in 39% yield over five steps. Finally, acetylation of the primary hydroxy group and subsequent removal of the acetonide provided the target

• unpleasant findings was a reaction of O-silyl-protected triol 12, which provided the bicycle 45 but only in a decreased yield of 40% (Table 1, entry 2). To show the usefulness of such cyclisation products, we have investigated the possibility of employing prepared tetrahydrofuran derivatives bearing suitable

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• group. Final removal of the TBDPS protecting group gave cyclopentane triol 159, which was esterified with varying equivalents of oleoside monomethyl ester peracetate 160 under Yamaguchi conditions [119][120] to give nudiflosides A (151) and D (13), respectively, thereby completing the synthesis and

Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

• Naoya Oku,
• Miyako Matsumoto,
• Kohsuke Yonejima,
• Keijiroh Tansei and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2014, 10, 1808–1816, doi:10.3762/bjoc.10.190

• -configuration of C12 to the chirality of C13, 3 was treated with NaOMe in methanol, and the obtained product triol 4 was converted to acetonide 5. The conformation of the 2,2-dimethyl-1,3-dioxolane ring in 5 was analyzed by NOESY and HSQC experiments, both of which confirmed a trans relationship of H12 and H13

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• the diol prior to acylation [32]. For the triple-chained tails, triol 15 was synthesised from tris(hydroxymethyl)methylamine (TRIS) and 4-pentynoic acid using ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), following a similar method to Pucci et al. (Scheme 2) [33]. TRIS has been used previously

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• -substituted analogues with interesting three-dimensional character, including chiral cyclopentane-1,2-diol and -1,2,3-triol derivatives. This unusual substitution pattern provides a useful starting point for the discovery of novel bioactive molecules. Keywords: diol synthesis; nucleoside; PreQ0

• ; stereoselective amine synthesis; triol synthesis; Introduction 7-Deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides are commonly found in nature playing a variety of roles such as building blocks of nucleic acids and tRNA, metabolites or antimetabolites [1]. Deazapurine ribonucleosides also show interesting

• -position of the heterocyclic core (systematic numbering) are scarce in the chemical literature and the methods available generally lack experimental information, making them unsatisfactory [18][19][20][21][22][23][24][25]. Inspired by the cyclopentane-1,2,3-triol motif present in noraristeromycin 5 (Figure

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• glucose-rings were connected via an enone linker. The dimer was then converted into a (partially protected) triol via a stereoselective reduction of the carbonyl group and highly selective cis-dihydroxylation of the double bond. The configuration at each new stereogenic center was determined by CD

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• phenylsulfone to get (4S,5S)-4-formyl-5-vinyl-2-oxazolidone, which was converted into 2a [18]. Merrer and co-workers used D-isoascorbic acid, which was transformed via (2R)-amino-1,3,4-triol to 2a [19]. Bergmeier et al. synthesized a chiral allyl alcohol from D-mannitol, which is converted to the azidoformate

• acetone–water (to cleave the anomeric carbon) followed by a treatment with sodium borohydride to give triol 6a as a viscous oil in 78% overall yield in three steps [34]. The primary hydroxy group of triol 6a was selectively monosilylated with t-butyldiphenylsilyl chloride to give 7a. Subsequently, the

• hemiacetal with NaIO4 and reduction with NaBH4 gave triol 6b,which was monosilylated with TBDPSCl to give 7b. Conversion of the secondary hydroxy group in 7b to azide 8b according to the Mitsunobu protocol, and deprotection followed by oxidation of the primary hydroxy group gave azido acid 10b. Finally

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• -coupled to iodobenzene, 4-trifluoromethyl-1-iodobenzene and 4-iodoanisole. The regioselectivities observed in the initial Diels–Alder reactions were maintained after cross-coupling (Scheme 14). More recently, new 2-boron-substituted 1,3 dienes containing diol and triol ligands were prepared under basic

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• was obtained in 90% yield (Scheme 10). Under these optimized reaction conditions other hydrogenolyses were studied. p-Bromophenyl-substituted triol 16 was transformed into the corresponding poly(hydroxy)aminooxepane derivative 31 in 73% yield. As expected, the bromo substituent of the aryl group was

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• 19 and 20 were obtained. In order to synthesize a model substrate without the rigid BDA-protecting group, compound 21 was treated with aqueous TFA to give a triol which was masked with three MOM-protecting groups (Scheme 3). Reductive cleavage of the pivaloyl group furnished alcohol 22. Mesylation or

• aqueous CH2Cl2 to release triol 36, which was masked with different protecting groups (MOM, TBS, Piv). After desilylation, the liberated alcohols 40, 41 and 42 could be esterified with various cyclic and acyclic model A rings to give the targeted rearrangement precursors A (Scheme 6, Table 2). The

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• 183. Complete reduction furnished triol 184, followed by mono-protection of the least hindered alcohol. The remaining alcohol moieties were then oxidized to the corresponding keto-aldehyde 185. A two-step procedure was employed to generate α,β-unsaturated oxindole-N-methoxide 187 [157][158]. Formation

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• the synthesis of RvD2 (1) is shown in Scheme 5. Sonogashira coupling [32][33] between 3 and 4 was very efficient giving the alkyne 18 in good yield. Removal of the acetonide was effected by treatment with HCl in MeOH to give the known triol 19 [9]. The final steps to 1 were similar with those

• be used immediately upon thawing. Alternatively, the triol 19 proved more stable than both RvD2 methyl ester (20) and RvD2 (1) and can be stored for longer periods prior to conversion to 1 which should be used rapidly for biological assessment to avoid degradation. Conclusion The total synthesis of

Triol-promoted activation of C–F bonds: Amination of benzylic fluorides under highly concentrated conditions mediated by 1,1,1-tris(hydroxymethyl)propane

• Pier Alexandre Champagne,
• Alexandre Saint-Martin,
• Mélina Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2013, 9, 2451–2456, doi:10.3762/bjoc.9.283

• under highly concentrated conditions, where solvents cannot interfere with the interaction between the organofluorine compound and the triol. Various benzylic fluorides react with secondary amines or anilines to form benzylic amines in good yields. Keywords: C–F bond activation; highly concentrated

• conditions; nucleophilic substitution; hydrogen bond; organofluorine; triol; Introduction The discovery of mild methods for the activation of C–F bonds is of high importance both from a fundamental point of view as well as for potential practical applications [1]. Specifically for aliphatic monofluorides, a

• work mostly as a triad of spatially and geometrically well-defined hydrogen bond-donating moieties. We therefore wondered about what would happen if these three moieties (water molecules) were covalently linked together in the form of a triol, which could help the three O–H functionalities to position

A protecting group-free synthesis of the Colorado potato beetle pheromone

• Zhongtao Wu,
• Manuel Jäger,
• Jeffrey Buter and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2013, 9, 2374–2377, doi:10.3762/bjoc.9.273

• , oxidation and stereoselective methylation using organometallic reagents are the key steps, affording (S)-1 in high enantiomeric purity and in gram quantities. In all these approaches, however, protection of the primary hydroxy group of the 1,2,3-triol substructure is required for the selective oxidation of

• of glycosides (Scheme 1) [14] and expected that the approach might also be applicable in the synthesis of (S)-1. Triol 3, with vicinal primary, secondary, and tertiary hydroxy groups should be a suitable substrate for chemoselective oxidation with catalyst 2, enabling a protecting group-free

• nerol [16][17][18] followed by stereoselective ring-opening with water would lead to the desired triol 3. Subsequently regioselective oxidation of 3 would provide (S)-1 in a concise 3 step route. The resulting synthesis would be interesting also for commercial application, moreover because the oxidation

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• used to set the C13 stereocenter. Additional efforts are needed to convert a fully oxygenated, ketone-containing triol into the critical epoxide fragment and to investigate the rearrangement of reductive coupling products. Structures of the ripostatins. Retrosynthesis of ripostatin A. Proposed

Development of an additive-controlled, SmI₂-mediated stereoselective sequence: Telescoped spirocyclisation, lactone reduction and Peterson elimination

• Brice Sautier,
• Karl D. Collins and
• David J. Procter

Beilstein J. Org. Chem. 2013, 9, 1443–1447, doi:10.3762/bjoc.9.163

• . Telescoped spirocyclisation/lactone reduction/Peterson elimination With an efficient process combining spirocyclisation and lactone reduction in hand, we proposed that manipulation of the triol products by Peterson elimination [43][44] could be added to the telescoped sequence. Crucially, Peterson

• elimination of triols 3 would result in removal of the silicon stereocontrol element used to control the stereochemical course of C–C bond formation. In early studies, treatment of triol 3b with t-BuOK gave vinyl cyclopentanol 5b in moderate yield [45], but the reaction suffered from poor reproducibility

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• system was also applied to the oxygenation of 1,3,5-triisopropylbenzene [17]. However, in this case the conversion of all isopropyl groups was far from being reached, with mono- and di-phenols being the major products, while the yield in benzene-1,3,5-triol was close to 1%. Sheldon and co-workers tested

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• -1,1,3-triol (IPB) was chosen due to its ease of preparation, better reactivity, and mild conversion conditions [27]. The Ugi-4CR involving carboxylic acid 9, DMB-NH2, formaldehyde and IPB resulted in intermediate 11 in 35% yield. A tandem DMB group cleavage/pyrrole-formation sequence under acidic

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• activity with an [α]D24 value of −51.6, indicative of an opposite sense of absolute configuration in comparison to the literature data given for (1S,2S)-dibenzyloxy γ-lactone ([α]D25 +60.1, c 1.0, CHCl3) [34]. From this, we can conclude, as seen in Scheme 2, that the more polar triol 12a-A obtained as a

Acceptor-influenced and donor-tuned base-promoted glycosylation

• Stephan Boettcher,
• Martin Matwiejuk and
• Joachim Thiem

Beilstein J. Org. Chem. 2012, 8, 413–420, doi:10.3762/bjoc.8.46

• understood by the presence of adjacent hydroxy groups on acceptors 1, 3 and 5, such as 4,6-diol and/or 3,4,6-triol structures, respectively. After deprotonation the negative charge is dispersed by hydrogen bonding of unreacted hydroxy groups and located predominantly at position 6 due to the higher acidity

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• protecting groups were then removed. First, the TBDMS ether was removed with acid to give the triol 19. Alternatively, 19 was formed directly in the dihydroxylation reaction by allowing a longer reaction time (20 h) after quenching with NaHSO3, leading to a similar overall yield (80% from 13). Attempted TBAF

• deprotection of the silyl ether in the dihydroxylation product 16 gave only a low yield of the triol 19. Subsequently, the benzyl ethers and nosylamide in 19 were cleaved under Birch reduction conditions to furnish the free Man(N4–6)Glc diglycoside 21. The other erythro configured pseudodisaccharide 15 behaved

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• %; in refluxing toluene) 79 was obtained in 85% yield. The three reaction steps leading from 78 to 80, i.e., RCM/hydroboration/oxidation, could be accomplished in one-pot to afford the product as a single isomer (all-trans triol). The prepared (+)-1-deoxynojirimycin (62) displayed spectroscopic data

• -methylphenylsulfonyl)azepane-3,4,5-triol (169). This compound shares a common configuration of the hydroxy groups with its lower cyclic homologue, 1-deoxymannojirimycin (DMJ, 63), a selective inhibitor of α-mannosidase I [82]. Lee et al. [83] also used RCM induced by the 1st-generation Grubbs catalyst 2 or the 2nd

• azepane-based iminocyclitols. Synthesis of hydroxymethyl-1-(4-methylphenylsulfonyl)azepane 3,4,5-triol (169). Synthesis by RCM of tetrahydropyridin-3-ol 171 and tetrahydroazepin-3-ol 173.

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• cephalosporolides. Gold(I) chloride in methanol induced the cycloisomerization of a protected alkyne triol with concomitant deprotection to give a strategically hydroxylated 5,5-spiroketal, despite the potential for regiochemical complications and elimination to furan. Other late transition metal Lewis acids were