Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• alcohol 143 with pivaloyl chloride [64] and subsequent dihydroxylation of the double bond in 144 according to the Sharpless protocol using AD-mix-β [65], furnished the required syn-diol 145 in 59% yield and >99% ee. The hydroxy groups were protected [66] as TIPS ethers 146 and treatment with DIBAL-H led

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• . eThe reaction was carried out using RhCl(PPh3)3 in THF at rt. Detection of metal-enolate and proposed mechanism of intramolecular cyclization. Synthetic route towards chiral necic acid lactone (2S,3S,4R)-2j. Conditions: a) CH3SO2NH2, AD-mix-β, t-BuOH, H2O. b) SO3·Py, Et3N, DMSO, CH2Cl2. c) DMAP, CH2Cl2

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• followed by addition of TBSOTf at low temperature successfully formed the (Z)-silyl enol ether 54. Application of the Sharpless asymmetric dihydroxylation, promoted by AD-mix-β, gave the expected β-(R)-hydroxy cyclopropyl product 55 in 84% yield with moderate diastereoselectivity (dr = 2). The formation of

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• transformed into (−)-101 using a three-step sequence. Upon iodination of (−)-101 produced iodide (+)-102 in excellent yield. Deiodination of (+)-102 followed by regioselective dihydroxylation with Sharpless’ AD mix-β reagent [64][65] provided diol (−)-103 as a mixture of stereoisomers. Significantly, the diol

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• with AD-mix-β provided an inseparable 82:18 mixture of diastereoisomers with the diol 196 as a major product. Silylation of the terminal hydroxy group was followed by mesylation of a secondary one to facilitate the piperidine ring closure triggered by hydrogenolytic removal of the chiral auxiliary to

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• conversion to the appropriate intermediates and subsequent acylation with lauric acid furnished the target compound. Keywords: AD mix-β; [bmim][PF6]; DDQ; HPA-12; lipase; Introduction Ceramides belong to the family of sphingolipids (SLs) and are synthesized de-novo in the endoplasmic reticulum (ER) [1

• (S)-4 with benzyl bromide (BnBr) and Bu4NI in the presence of NaH produced compound 6 (Scheme 2). This was subjected to asymmetric dihydroxylation (ADH) using AD mix-β [K2OsO2(OH)4 and (DHQD)2-PHAL]. The reaction proceeded predominantly from the α-face, resulting in the formation of the 1,3-anti diol

• 7a and 1,3-syn diol 7b in a 91:9 ratio (based on the isolated yields of 7a and 7b, separated by column chromatography). Previously the ADH reaction of a homologue of 6, bearing a methyl substitution and a hydroxy group (instead of benzyloxy group) with AD mix-β also produced the corresponding α

Systematic synthetic study of four diastereomerically distinct limonene-1,2-diols and their corresponding cyclic carbonates

• Hiroshi Morikawa,
• Jun-ichi Yamaguchi,
• Shun-ichi Sugimura,
• Masato Minamoto,
• Yuuta Gorou,
• Hisatoyo Morinaga and
• Suguru Motokucho

Beilstein J. Org. Chem. 2019, 15, 130–136, doi:10.3762/bjoc.15.13

• characterisations of 2a and 2d remain unreported. Very recently, Wang et al. synthesised 2a and 2d using OsO4, and exclusively 2d using Sharpless AD-mix-β [21] as a catalyst (Scheme 1a) [16]. In contrast to that, Mori reported that (R)-dihydrolimonene, the structure of which is similar to LM, was oxidised using

• Sharpless AD-mix-β to afford a 2a-type main product (Scheme 1b) [22]. Hao et al. also reported the synthesis of 2a and 2d using OsO4 (Scheme 1a) [23]. However, the NMR data of 2a and 2d were not consistent with those [16] reported by Wang. Moreover, they referred to a published paper [24] for the assignment

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• subjected to a Sharpless asymmetric dihydroxylation with AD-mix-α in t-BuOH/H2O (1:1) at 0 °C for 24 h furnishing syn-2,3-dihydroxy ester 19 in a high yield of 92%. For the synthesis of syn-2,3-dihydroxy ester 20, AD-mix-β was employed. Debenzylation of diol 20 with Pd–C and H2 at room temperature produced

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• across the C-4/C-5 alkenyl group exclusively, but the introduction of the fluorine atom at C-6 lowered the selectivity (10:11) to 5:1 with AD-mix-α and 4:1 with AD-mix-β. Nevertheless, de novo stereodivergent approaches are conceptually important and pave the way to wider ranges of more unnatural species

• using the improved Sharpless conditions with the newer AQN based ligands, producing excellent ee’s for both enantiomers of the diol, 95% for the enantiomer derived from AD-mix α, and 97% for the enantiomer from AD-mix β (Table 1). The corresponding isolated yields under these conditions were 54% and 56

• are represented by combinations of components, for example (DHQD)2 PHAL, present in AD-mix β. Diisopropyl L-tartrate (30) used as a chiral modifier for NMR determination of ee. Partial 19F{1H} NMR spectra (376 MHz, L-(+)-DIPT/CDCl3, 300 K) spectra of (a) racemate 28c, (b) diol 28b and (c) 28a under

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• conditions [20]. Similarly, alcohol 4 could be converted to 4′. Alcohol 4 was methylated using MeI and t-BuOK to produce 5 in nearly quantitative yield (Scheme 3). Sharpless asymmetric dihydroxylation [21] of olefin 5 using AD-mix-β in a 1:1 mixture of t-BuOH/H2O at 0 °C over four days afforded diol 6 with S

• dihydroxylation of 5′ using AD-mix-β afforded desired diol 6′ in 82% yield. Subsequently, treating 6′ with TBSOTf afforded 7′. Selectively deprotecting the primary hydroxy group using CSA in methanol at 0 °C for 45 min provided alcohol 8′ in 60% yield, as well as a 15% yield of diol 6′ that could be recycled to

• ,THF, rt, 96%; (b) AD-mix-β, t-BuOH/H2O, 0 °C, 80%; (c) TEMPO, NaClO, CH2Cl2, −5 °C. AD = asymmetric dihydroxylation, TEMPO = 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical. Reagents and conditions: (a) PhCH(OCH3)2, PPTS, CH2Cl2, rt; (b) DIBAL-H, CH2Cl2, 0 °C, 76% in two steps. PPTS = pyridinium p

Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

• Hiroyoshi Takamura,
• Takayuki Fujiwara,
• Isao Kadota and
• Daisuke Uemura

Beilstein J. Org. Chem. 2013, 9, 1931–1935, doi:10.3762/bjoc.9.228

• to the Sharpless AD [15] with AD-mix-β to furnish the C79–C97 fragment 27 in 72% yield as a single diastereomer (Scheme 5). The configuration of the resulting two vicinal hydroxy groups at C93 and C94 of 27 were unambiguously confirmed by the modified Mosher method, respectively (see Supporting

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

• reaction. By employing AD-mix-α under the above reaction conditions, 6d gave rise to a 69:31 mixture of 12d-A and 12d-B in 48% yield, leading to 12a-A and 12a-B through hydrolysis under basic conditions, respectively, whereas the use of AD-mix-β resulted in predominant formation of the undesired

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• ). Asymmetric dihydroxylation with AD-mix-β on 11 and subsequent acid-catalyzed cyclization with camphorsulfonic acid (CSA) resulted in THF ring-containing building block 12, which was converted into alkyne 13. The alkylation of iodide 14 with the sodium enolate of 15 afforded 16. Transformation of 16 following

• ,19S,20S)-cis-murisolin (112), and (15R,16R,19R,20S)-murisolin A (121) (Scheme 18). The mono-THF moieties were synthesized from epoxy alcohol 122 by using Sharpless AD-mix-β for the threo-trans-threo THF moiety 123, a AD-mix-β followed by the Mitsunobu reaction for the erythro-cis-threo THF moiety 125

• controlled double cyclization of 230 allowed the selective formation of a single diastereomer 231 in one step, thus providing general access to annonaceous acetogenins containing trans/threo/trans or cis/threo/cis bis-THF core structures. Desymmetrization of diene 231 with AD-mix-β provided the known triol

An asymmetric synthesis of all stereoisomers of piclavines A1-4 using an iterative asymmetric dihydroxylation

• Yukako Saito,
• Naoki Okamoto and
• Hiroki Takahata

Beilstein J. Org. Chem. 2007, 3, No. 37, doi:10.1186/1860-5397-3-37

• ) obtained for AD of terminal olefins are lower than for trans disubstituted olefins. However, it is expected that iterative AD terminal olefins will give products with high ees based on the following consideration. The first AD (AD-mix-β) of 5 produces major and minor enantiomers, 6 and ent-6, which are