Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• unit. The final steps of this synthesis involved alcohol deprotection, double bond hydrogenation and oxidation, and allowed the total synthesis of (−)-nitidasin (93) in 27 steps. Naupliolide (97) was first isolated from the aerial parts of Nauplius graveolens in 2006. This tetracyclic natural product

• allowed to install the cyclopropane ring thanks to the allylic alcohol. The latter was submitted to Ley oxidation, then deprotection and removal of the obtained alcohol gave the [5-8-5] advanced intermediate 184 (Scheme 36). The stage was set for the further functionalization to synthesize hypoestin A

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• compound 1, swapping the order of purification and deprotection severely decreased the yields (data not shown). The sn-1-acyl isomer 3a exhibited a positive rotation ([α]D22.3 +5.5 (c 0.30, MeOH)) while the sn-3-acyl isomer 3b gave a negative rotation ([α]D22.5 −5.5 (c 0.30, MeOH)), suggesting that

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• Downstream chemistry and further applications: deprotection, cleavage or further functionalization of 1,4-dithianes In organic synthesis, the deprotection of 1,3-dithianes has a reputation of being a troublesome reaction. In the chemical literature, there are probably well over a hundred distinct procedures

• to be found for the deprotection of dithioketals [113]. This is likely because none of them is really generally applicable, and synthetic chemists have often found themselves in a place where they were in need to find an alternative procedure for their particular substrate. Nonetheless, the distinct

• mixtures of the desired and undesired positional alkene isomer could be obtained. We believe an outstanding challenge in the field of chemical synthesis is to find mild and catalytic deprotection chemistries for dithiane-type systems, be they reductive, hydrolytic or oxidative. In particular, a more

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• an electrochemical method to provide the desired coupling towards 56 in 62% yield. Radical reduction by Mn(dpm)3 afforded stypodiol (57) after BBr3-mediated deprotection. Nickel-catalyzed coupling under a Weix procedure [31] was selected in order to elaborate the cores of taondiol (53) and chevalone

• conditions of the Heck reaction to common scaffold 70 proved unsuccessful. Screening of several reaction conditions on different analogues led to the conclusion that reduction of the C8-carbonyl side and acetal deprotection to 71 are essential in order to create the 6/6/5/6-carbocycle in the presence of Pd2

• assigned after deprotection with BBr3 to complete the first total synthesis of dysiherbol A (79). Total syntheses of (+)-jungermatrobrunin A (89) and related congeners (Lei 2019) [40]: The ent-kaurane diterpenoids constitute a highly diverse class of structurally complex natural products possessing

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• TBS deprotection giving the bicyclo[3.2.1]octane subunit with a good yield of 74%. A sequence involving diastereoselective reduction of ketone 24 with SmI2, Appel reaction to convert the primary alcohol to the corresponding primary alkyl iodide followed by a MOM protection of the secondary alcohol

• a TBS ether, α,β-desaturation, dithiane addition, MOM protection and dithiane deprotection. The fragment 25 was lithiated with t-BuLi and the fragment 29 was then added, forming the coupling product as a 5:5:1:1 separable mixture of diastereomers (Scheme 5). The desired diastereomer 30 was isolated

• was selectively reduced in the presence of LiEt3BH, while the Peterson adduct was eliminated concurrently, upon heating. Finally, treatment with H2SO4 allowed total deprotection of the MOM ethers, leading to the formation of principinol D, in complete correspondence with reported spectral data

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• two options for the generation of 4-ethoxy-2,3,6-triaminopyridine (9). One possibility comprised the deprotection of the dicarbamate 5 with potassium hydroxide giving the diamine 6, followed by azo coupling with the diazonium salt obtained from aniline and sodium nitrite to give azo compound 7

• methanol (20 mL), then 5% hydrochloric acid (5 mL) was added and stirred for 2 hours at 50 °C. After complete deprotection (TLC reaction control!), the solvent and all volatiles were removed under reduced pressure and the crude residue was suspended in dichloromethane (6.5 mL). Afterwards, di-tert-butyl

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• conditions gave the secondary side peracetylated 6 in a high yield. The selective deprotection of silyl groups, yielding compound 7, was also performed standardly using BF3O·Et2O. Our new procedure is based on the methylation of this acetyl-protected β-CD 7 using a DIPEA/methyl tosylate mixture without

• selectively methylated rims The important part of this work was proving the structure of the synthesized compounds because we worked with non-symmetrical CDs; moreover, we used protection–deprotection methods for partial methylation, so we could expect a cleavage or even migration of protective groups

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• deprotection of the silyl group was accomplished in the presence of potassium carbonate (K2CO3) and methanol to provide the terminal alkyne 5 in 96% yield in two steps. The iodoarene 8 [12][16] was facilely synthesized from sesamol (6) via methylation and iodination in an overall yield of 67%. With the

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• determined using the modified Mosher’s method [21]. Protection of diol 25 by tert-butyl(dimethyl)silyl (TBS) group followed by selective deprotection of the primary alcohol led to 27. Finally, acid 7 was obtained from alcohol 27 through the same two-step oxidation used to obtain compound 10. Having

• 29. Then, five rounds of DIC/Oxyma-mediated amidation [22] and Nα-deprotection with piperidine led to resin-bound peptide 5. Treatment of 5 with TFA/CH2Cl2 1:99 released 30 into the solution without unmasking the acid-labile protecting groups of the side chains. Subsequently, peptide 30 was cyclized

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• gives access to 6A-mono- and 6A,D diol (3) in high yields and purity, and by extension of this method further deprotection on the primary [10][11][12] and secondary rim can be made [13][14][15]. The reaction of 2 with DIBAL leads quite rapidly to diol 3 and then much slower to triol 4 and tetrol 5

• . These methods are so useful because virtually any chemical modification at the deprotected sites can be made followed by global deprotection of the O-benzyl groups with hydrogenolysis. Recently, we observed a strong substituent effect when substituted benzyl groups were used in these reactions with

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• relative to the proton H-2. For the synthesis of the aminocyclooctanetriol 13, hydrogenation of the azido alcohol 11 gave amine 12 in 95% yield (Scheme 2). Subsequent, benzyl deprotection with BCl3 of 12 resulted in the target compound 13 in 85% yield. The structures of compounds 12 and 13 are completely

• a positive NOE clearly indicates that the protons H-2/H-7 should have a cis configuration relative to the protons H-1/H-8. Finally, benzyl deprotection with BCl3 of 14 afforded the product 16 in 84% yield. The structure of 16 was assigned on the basis of NMR spectroscopy. Conclusion In summary, we

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• . Hydrazinium dihydrochloride was isolated in some cases (confirmed by X-ray, mp, and FT-IR data) demonstrating the degradation of the heteroadamantane cage. Deprotection of Cbz derivatives by hydrogenation over Pd–C was more productive. Thus, hydrogenolysis of product 8b delivered the 1N,2O-TAAD derivative 15

• , deprotection reactions were performed at low temperatures to prevent degradation of the aminal fragments. Indeed, treatment of Bn-4c with hydrochloric acid at 0 °C resulted in a substitution of one NNH2 unit with the oxygen atom producing product 22, having a hitherto undescribed 4-oxa-1,6,10-triazaadamantane

• ) Fragment of 1H NMR spectra of Bn-4c in DMSO-d6 and CD3OD. A general strategy for the assembly of TAAD derivatives. Synthesis of acyclic precursors to 3N-TAADs, 2N,1O-TAADs, and 1N,2O-TAADs. Synthesis of 3N-TAADs, 2N,1O-TAADs, and 1N,2O-TAADs. *Yield based on compound 14. Deprotection of TAAD 8b and

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• deprotection with concomitant azide reduction was completed using hydrogen and Pd/C and Pd(OH)2/C catalysts, affording 13 as the disodium salt in 90% yield, after anion exchange chromatography. Synthesis of 6-deoxy-6-thio-ᴅ-mannose 1-phosphate (18) was completed from 14 via C6 substitution with thioacetate and

• diffuse intermolecular C–H···O contacts involving the phosphate and acetyl oxygen atoms. Deprotection of 16 was completed in two steps, first using hydrogenolysis with Adam’s catalyst (PtO2), followed by removal of the acetate protecting groups with Et3N/H2O/MeOH, and furnished the target glycosyl 1

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• ]. DMP oxidation of α-hydroxyester 21 and subsequent cycloisomerization led to the desired cyclization product 23 via transition state II in a dr of 5:1. Final deprotection gave preussochromone A (24). (−)-Preussochromone D A similar approach was chosen in the synthesis of the structurally related

• 27. Subsequent oxidation gave α-ketoester 28 which was used in an intramolecular, Lewis acid-mediated aldol reaction, presumably via tridentate complex transition state III, to give diol 29 as a single diastereomer. Inversion of the secondary alcohol and deprotection gave preussochromone D (30

• precursor for an intramolecular Friedel–Crafts cyclization (Scheme 9) [24]. Therefore, phenylacetaldehyde 52 was converted to the alcohol 53, which was esterified with the α-ketoacid 54 to give ketoester 55. Grignard addition to the keto carbonyl and subsequent TBS deprotection delivered the tertiary

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• blocks can reduce the number of steps in the total synthesis. However, it requires manipulation of the anomeric leaving groups and deprotection of the protected hydroxy group at the 4-position prior to glycosylation. Although automated electrochemical assembly, which is a one-pot iterative synthesis of

• examined. By repeating cycles in one pot, the modified method enabled us to prepare longer oligosaccharides up to the octasaccharide. Further optimizations of reaction parameters, such as concentration, size and shape of electrodes for large-scale production of oligosaccharides, and deprotection of

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• challenging and often requires prefunctionalization of the substrate monomers, costly metal ligands, or tedious protection–deprotection steps [6][7][8][9]. With the advance of biosynthetic studies on natural products, a number of enzyme classes that are responsible for the dimer formation have been identified

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• method is to introduce alkyl formate, formacyl, methylene or their equivalents to amines, followed by reduction to give monomethylamines [44][45][46][47][48][49][50][51]. Protection/methylation/deprotection strategies have also been developed for the preparation of monomethylation objects, which are

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• generated in situ from propiophenone, and second, the deprotection of propiophenone α-thioesters in the presence of perfluoroalkyliodides and subsequent oxidation of the formed perfluorothioether into the sulfone. However, none of these proposed pathways gave yields high enough for the reaction to be

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• prefunctionalization and deprotection synthetic procedures. Based on the logical concept of protecting groups, noncovalent interactions can be considered, because they can be built up in situ and are weak enough to let the substrate dissociate from the “protecting template” easily, omitting the complicated

• prefunctionalization and deprotection processes. Moreover, functional groups that are not suitable for being functionalized with protecting groups can also be incorporated into the noncovalent protective systems. Actually, the molecular container has been applied to work as a noncovalent protective module. In this

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• ligand 2,2’-bipyridyl (Scheme 1). The reaction utilizes KOH as the base, since it provides the suitable deprotection of arylynols 3 during the synthesis of the terminal arylalkynes. The optimized conditions revealed that 10 mol % of Fe catalyst/ligand at 140 °C for 48 h afforded the maximum yields of the

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• the deprotection step with CH3OH/triethylamine/H2O 4:1:5 [26], triethylammonium ions were exchanged upon treatment with Amberlite IR 120 (Na+ form) and compounds 3a–h were obtained in excellent yield and purity without further purification. Chemical structures and reported activities of viral (A

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• ratio was also very high. Only prolonged reaction times (>18 h) led to epimerization of the rearranged peptide. With rearranged tetrapeptide 9b in hand, esterification with pentafluorophenol (Pfp) gave Pfp ester 10, which should readily cyclize after Boc deprotection (Scheme 4). Treatment with HCl in

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• – deprotection, deprotonation and coupling – in two pots. Here, we report a more convenient approach for PEG synthesis featuring the use of a base-labile protecting group such as the phenethyl group. Using this approach, each elongation of PEG can be achieved in two steps – deprotection and coupling – in only

• one pot. The deprotonation step, and the isolation and purification of the intermediate product after deprotection using existing approaches are no longer needed when the one-pot approach is used. Because the stepwise PEG synthesis usually requires multiple PEG elongation cycles, the new PEG synthesis

• ][26]. Perhaps, the most widely used methods in academia and in industry involve the use of monomers such as compound 1, which contain the acid-labile DMTr protecting group. PEG elongation is achieved by deprotection under acidic conditions, purifying the intermediate, and setting up a separate

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• contrast, photorelease systems based on C–C or C=C bond photocleavage are quite rare [14][15]. We recently reported a vinylogous analogue of this photo-deprotection process, which allowed photocleavage of alkenyl sp2 C–X bonds, rather than benzylic sp3 C–X cleavage [16][17]. We now report that further

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• -OH (4 equiv), HATU/coupling reagent (4 equiv) and DIPEA (8 equiv) in DMF (20 mL). The coupling mixture was filtered and the resin was washed with CH2Cl2 (10 mL × 5) and CH3OH (10 mL × 5). General procedures for deprotection of Fmoc: The loaded resin was treated with a solution of 20 vol % piperidine