Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• biosynthesis of reduced polyketides in bacteria by modular polyketide synthases (PKSs) proceeds with exquisite stereocontrol. As the stereochemistry is intimately linked to the strong bioactivity of these molecules, the origins of stereochemical control are of significant interest in attempts to create

• this approach to provide answers to fundamental biological questions. Keywords: chemical biology; polyketide synthases; reduced polyketides; stereocontrol; Introduction Reduced polyketides and their derivatives form the basis for a number of medicines in current clinical usage, notably anti

• so in principle, 1024 (210) different stereoisomers are possible. Yet, nature reliably assembles only one stereoisomer (at least at detectable levels), at once revealing the strict stereocontrol underpinning the pathway and the importance of synthesizing this particular version. Indeed, the crystal

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• the reaction intermediate is a radical that prefers to be axial. On the other hand, with acetate protective groups, the addition of deuterium occurred predominantly from the β-side [45][46]. The principle of conformational stereocontrol was also used for the stereoselective addition of carbon radicals

• C-glycosides it has been possible to obtain conformationally derived stereocontrol so that persilylated donors adopting a 1C4 conformation give the β-products. However, for O-glycosylation, this type of selectivity has been difficult to achieve. Some very useful stereoselectivities are obtained with

Strategies in asymmetric catalysis

• Tehshik P. Yoon

Beilstein J. Org. Chem. 2017, 13, 63–64, doi:10.3762/bjoc.13.8

• synthetic problems. The articles collected in this Thematic Series for the Beilstein Journal of Organic Chemistry provide a snapshot of both types of efforts. Several of these papers report new catalyst designs or relatively new concepts in catalytic stereocontrol. Others document the application of

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• coupling in high yield with good stereocontrol [38][39][40]. With the auxiliary controlled alkylation of enolates products being analogous to radical hetero-coupling can be synthesized [41][42]. However, both methods require costlier reaction conditions as inert gas, dry solvents and LDA as reagent, and

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• derivatives of the D-xylo and L-ribo series, respectively C-4 and C-2 epimers of the L-arabino series. Based on these aldol condensations together with the work previously performed on the L-arabino [33] and L-lyxo [34] series, a working mechanism is presented to explain the complete stereocontrol over the

• formation of the two new stereogenic centres (red in Scheme 1). Furthermore, the stereochemical outcome of the intermediate inososes reduction by using different reagents, namely the stereocontrol over a third stereogenic centre (green in Scheme 1), is also reported. Results and Discussion The aldol

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• efficiently converted into 4ga and 4ha with rigorous relative and absolute stereocontrol (Table 2, entries 15 and 16). The absolute configuration of 4ca was unequivocally determined by X-ray crystallographic analysis (Figure 2), and the stereochemistry of the remaining examples was assumed to be analogous

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• . The resulting intermediate undergoes proton transfer and elimination of the phosphonium moiety, resulting in product 30 and regeneration of the catalyst. This exceptional demonstration of stereocontrol requires that the catalysts precisely organize both the electrophilic and nucleophilic reactants to

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• and natural products as well as for the mild functionalization and derivatization of diene-containing natural products [1][2][3][4][5][6][7][8][9][10]. The reversibility of this reaction plays a considerable role in both the observed regio- and stereocontrol of the nitroso Diels–Alder reaction

Experimental and theoretical insights in the alkene–arene intramolecular π-stacking interaction

• Valeria Corne,
• Ariel M. Sarotti,
• Carmen Ramirez de Arellano,
• Rolando A. Spanevello and
• Alejandra G. Suárez

Beilstein J. Org. Chem. 2016, 12, 1616–1623, doi:10.3762/bjoc.12.158

• an element of stereocontrol in highly selective chemical transformations has been widely explored [9]. In this context, as part of our continuous interest in the development of new tools for asymmetric synthesis using levoglucosenone (a biomass-derived chiral enone) [10][11][12][13][14][15], we

• aromatic rings. This can be useful in several fields, such as supramolecular chemistry, biology and material science and, in particular, in the area of asymmetric synthesis for the rational design of new elements of stereocontrol. Intramolecular aryl–vinyl π-stacking interaction of a levoglucosenone

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• stereocontrol, while Tyr157 and Lys161 participate in pre-orienting NADPH for transfer of its pro-S proton [27][32]. The resulting secondary alcohol 43 is processed similar to its enantiomer 39 in actinorhodin biosynthesis to give (R)-DNPA (46) and finally graniticin (36) after tailoring. It has been proposed

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• block 1 was designed (Figure 2). A levulinoyl (Lev) ester was chosen as temporary protecting group (TPG) since the Fmoc (fluorenylmethoxycarbonyl) group led to a loss of stereocontrol during glycosylations with this glucuronic acid (GlcA) building block (data not shown). Glucose building blocks 2 and 3

• glucose building block. This monomer did not suffer from a loss of stereocontrol as was observed in the case of the similarly protected GlcA building block. The desired trisaccharide 5 was observed as the main product from the automated synthesis by HPLC analysis (Figure 5). The Lev protecting group had

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• -controlled Michael reaction remained present. Accordingly, we chose to probe reactivity and establish relative stereocontrol using a close model system comprising pronucleophile 8 and furanyl nitroolefin 11 (Scheme 1). The δ-valerolactone pronucleophile 8 was synthesised by the enolate acylation of δ

Bifunctional catalysis

• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1079–1080, doi:10.3762/bjoc.12.102

• effect of the two complementary functional groups can lead to new reactivity and stereocontrol in reactions that were previously challenging or unprecedented. With multiple points of diversity in the two functional groups and the chiral scaffold, these catalysts can be readily tuned to optimise

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• catalysts were not efficient in terms of stereoselectivity. However, good results regarding both, yield and stereocontrol, were observed when the Rawal catalyst C1 [60][61] was employed (Scheme 2). Under the optimized conditions the reaction, as shown in Scheme 2, worked equally well regardless of the

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• enabled a high degree of regio- and stereocontrol necessary for the introduction of heteroatomic substituents at C-2, C-3, and C-4. The synthesis of the analogs 6–8 has not yet been reported to our knowledge, while the synthesis of 1, 4 and 5 represents an alternative to the published procedures [2][20

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• acetylated salidroside 22 from moderate (ZnO–ZnCl2, 49%) to good yields (DDQ–I2, 61% and ZnO–I2, 63%) with strict β-stereocontrol. On the other side, the glucosylation of p-O-acetylated coniferyl alcohol 12 with bromide 13 failed under these conditions. Coniferyl aldehyde 24 was detected and isolated as a

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• , respectively, in excellent yields and stereoselectivities (Scheme 13) [24]. Computational studies were employed, in order to support the mechanistic pathway and the origins of stereocontrol. Secondary amino-thioureas as organocatalysts promoting asymmetric transformations that lead to a six-membered ring In

• , Enders and co-workers described the three-component domino Michael–Michael aldol reaction between β-ketoesters 153, nitroalkenes 77 and α,β-unsaturated aldehydes 154, producing heavily substituted cyclohexanes 155 containing six contiguous stereocenters with excellent stereocontrol (Scheme 49) [70]. In

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• stereocontrol [6][7][8][9][10][11][12]. Maleimides are also good nucleophilic precursors in the MBH reactions and in 2013, Chimni developed an asymmetric MBH reaction of isatins and maleimides with excellent enantioselectivity [13]. Later, the same group expanded this strategy to isatin-derived ketimines under

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• the diastereoselectivity. We had anticipated that the binding of the Lewis acid to the free alcohol, followed by intramolecular activation of the aldehyde, would establish a cyclic transition state, thereby enabling better stereocontrol. It is indeed well-known that the Ugi reaction does not proceed

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• advantage of a chiral (R)-BINOL-bridge to link the two aromatic acids and obtained the coupling product with excellent stereocontrol (up to 100% de) (Scheme 1) [16][17][18][19]. In 1998, Martin et al. [20] applied this strategy to the asymmetric intramolecular biaryl coupling of sugar derivatives carrying 2

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• therefore access to any stereoisomer at will from the same set of starting materials with full absolute and relative stereocontrol is not trivial. Previous reports show that the diastereoselection can be directed by different approaches that include the modification of reaction conditions [7][8][9], the

• involved changing the solvent to 1,2-dichloroethane [27]. As it happened in the previous case, we could observe that the reaction performed well in all cases tested and, in general, with a similar level of chemical efficiency and stereocontrol, although in comparison with the 4-catalyzed version

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• naturally occurring terpenoids is the reductive amination under Leuckart–Wallach conditions (see Scheme 2, pathway I) [39]. This method was applied to convert 2 to N-alkyl substituted menthylamines [40]. However, a significant disadvantage of this method is the lack of stereocontrol and partial inversion of

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• phosphorothioates is reason enough to investigate the synthesis of P-chiral phosphorothioates [13][14][15][16][17][18][19]. However, none of the reported methods seem to allow for routine, high-yield synthesis with high stereocontrol [20][21][22][23]. The extension to phosphorothioate RNA for applications of RNA

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

• metal-catalysed carboetherification reactions [16][17][18] and intramolecular oxycarbonylations of alkenes [19][20][21] are of particular importance. Although, many of these synthetic routes have showed their potential, there is still an area for improving the scope and stereocontrol of the new

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

• employed in organic synthesis primarily as stabilized anionic nucleophiles in addition reactions to electrophilic substrates with good to excellent stereocontrol. The products obtained from these reactions were used as key building blocks in the total synthesis of a variety of structurally highly diverse

• synthetic transformations [1]. This chiral phosphonamide typically yields reaction products with excellent stereocontrol, which are easily isolated as diastereometrically pure or highly enriched compounds. Many are crystalline solids that can be purified further by recrystallization. Diazaphosphorinane 3

• high level of stereocontrol (Scheme 4) [37][38][39][40]. Thus, vicinal and quartenary carbon centers can be obtained in high diasteromeric purity by conjugate additions of allyl, crotyl, and cinnamyl-derived anions to Michael acceptors such as enones, lactones, lactams, and α,β-unsaturated esters