Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• [21] between two equivalents of ethyl nitroacetate (4) and styrene (15), gave the isoxazoline 16 in a 72% yield as a latent α-amino ester [22][23][24]. From this compound, a reductive cleavage of the isoxazoline ring was initiated using palladium over charcoal and a large excess of ammonium formate in

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• benzyltriethylammonium tetrathiomolybdate, [C6H5CH2NEt3]2MoS4 over 4–12 hours produced the desired hydroxy sulfides in yields of 48–90% (Scheme 24). The authors proposed that the reaction proceeds via a reductive cleavage of the in situ-generated disulfide (RSSR). The resulting thiolate then undergoes thiolysis of the

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• bisoxazoline ligand, diazo compounds 42’ with various electron-withdrawing groups were efficiently oxyalkynylated affording highly enantioenriched propargyl esters 44 (Scheme 23). Subsequent reductive cleavage of the ester gave direct access to enantiopure propargyl alcohols. Besides EBX reagents

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• condensation of alkyl-substituted silyl ketene acetals (32) with enantioenriched α-2,2,6,6-tetramethylpiperidinyl-β-benzyloxypropionaldehyde (33) in presence of TiCl2(OiPr)2 to give the β-hydroxyester 34 that is diastereomerically enriched [75][95]. Reductive cleavage of the 2,2,6,6-tetramethylpiperidinyl (TMP

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• conditions for their cleavage. Secondly some glycosyl oxazolines are also prone to reductive cleavage by catalytic hydrogenation [41], presenting a significant further limitation as to which OH-protecting groups may be employed. Most of the reports in the literature have therefore used a protecting group

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• dimer was then extended to the trimer by another cycle of detritylation, precipitation, coupling and precipitation. During reductive cleavage of the disulfide bond to release the fully protected trimer from the support, unfortunately the loss of the 5'-DMTr group was observed. To overcome this hurdle

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• derivative 5 in reasonable yield. Later on, hydrogenolytic cleavage of the generated benzylamine-type group at C1 should give the desired 1-methyl moiety. Related reductive cleavage reactions have been published earlier by Möhrle [20] for phenolic Mannich bases in the course of the total synthesis of the

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

• Chandra Kant Maurya,
• Avik Mazumder and
• Pradeep Kumar Gupta

Beilstein J. Org. Chem. 2017, 13, 1184–1188, doi:10.3762/bjoc.13.117

• systems and by the breakdown of sulfur-containing amino acids and lignin [4][5][6][7]. In laboratory, thiols can be synthesized from alcohols [8][9], alkyl halides [10], alkenes [11] and through reductive cleavage of organic thiocyanates (or simply thiocyanates hereafter) by means of alkali metals–ammonia

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• an original sequence involving a reductive cleavage of the auxiliary. Synthesis of the southern fragment The same southern fragment 6 was independently chosen by the Menche group in their total synthesis of archazolid A and by the Trauner group in their total synthesis of archazolid B. Both groups

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• -BuOH could act as a proton donor and so prevent the olefin isomerization. Alkali metals can also be used in suspension. As mentioned above, highly dispersed potassium over neutral alumina (K/Al2O3) in hexane is able to effect the reductive cleavage of alkylnitriles [18][34]. Zárraga et al. described an

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

• /b to diesters 26a/b/c–29a/b/c (n.d.: not determined). Reductive cleavage of 30a–c to 8-phenylmenthol (3) and 31a–c. 13C NMR data of compounds 23, 24 and 25. Facial selectivities for 26–29. Comparison of the diastereoselectivity in hetero- and homo-coupling reactions. Supporting Information

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• directly the alcohol 28 in 41% yield through concomitant reduction of the intermediate allylic chloride and cleavage of the silyl protecting group. The reductive cleavage of tert-butyldiphenylsilyl ethers by LiAlH4 has been previously noticed [39]. Jones oxidation straightforwardly completed the synthesis

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

• . Having played a key role in the Michael addition reaction and the nitro-Mannich lactamisation cascade, at this stage the nitro functionality had fully served its purpose. Accordingly, traceless reductive cleavage of the nitro group [22] using tributyltin hydride and AIBN was carried out to afford

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• -catalyzed and base-mediated cyclization of carbonate 71 [45]. Reductive cleavage of the sulfone using aluminium amalgam afforded a ketone, which was converted to an exocyclic double bond by treatment with Tebbe’s reagent [42]. In order to convert the methoxy acetal to the corresponding lactone, without

Preparation of a disulfide-linked precipitative soluble support for solution-phase synthesis of trimeric oligodeoxyribonucleotide 3´-(2-chlorophenylphosphate) building blocks

• Amit M. Jabgunde,
• Alejandro Gimenez Molina,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2015, 11, 1553–1560, doi:10.3762/bjoc.11.171

• -protected oligodeoxyribonucleotide trimer 3’-pTpdCBzpdGibu-5’ as its 3’-(2-chlorophenyl phosphate) was achieved by reductive cleavage of the disulfide bond. Keywords: disulfide linker; oligodeoxyribonucleotides; phosphotriester chemistry; precipitation; soluble support; Introduction Synthetic nucleic

• introduced in a 5´-O-(4-methoxytrityl) protected form to prevent detritylation during the reductive cleavage of the trimer from the support. Experimental General: NMR spectra were recorded on a Bruker Avance spectrometer (500 or 400 MHz) at 25 °C. Chemical shifts are given in ppm and referenced relative to

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• SmI2 reduces N–O bonds [172][175], the 1,4-addition product was isolated as the amide, which resulted from the reduction of the N-OMe bond. Use of smaller quantities of SmI2 in the reaction produced only the reductive cleavage product (N–H) with no cyclization. 2.4 Lewis acid-catalyzed ECA reactions

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

• prepared from amide bond formation between the amine IV and acrylic acid (for IIIa) or butenoic acid (for IIIb). The remaining hydroxy group at C-4 could possibly be generated by a reductive cleavage of the N–O bond in 6. Thus, treatment of compound 6 with Zn/AcOH proceeded well to give the all-cis

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• understanding of this unexpected result the reductive cleavage was examined with the simpler bicyclic 1,2-oxazine derivative 12a. Here the unexpected bicyclic compound 24 was isolated as major product in 79% yield together with the desired aminopyran derivative 25 in 14% yield. It was observed by 1H NMR

• methanol/THF. In summary, by optimizing the protective group strategy and the reductive cleavage methods we were able to prepare the desired rigid p-terphenyl-linked carbohydrate mimetic 30 in twelve steps starting from D-isoascorbic acid, but in only six steps with respect to crucial intermediate 4. The

• , rt, 24 h. Synthesis of N-benzylated p-terphenyl derivative 21 by Suzuki cross-coupling of 12a with 20 and subsequent reduction with zinc. Conditions: a) Pd(PPh3)4, 2 M Na2CO3 aq, THF/DMF (8:2), 70 °C, 48 h; b) Zn, AcOH, THF, 60 °C, 18 h. Attempted reductive cleavage of the N–O bond of compound 21 by

Allenylphosphine oxides as simple scaffolds for phosphinoylindoles and phosphinoylisocoumarins

• G. Gangadhararao,
• Ramesh Kotikalapudi,
• M. Nagarjuna Reddy and
• K. C. Kumara Swamy

Beilstein J. Org. Chem. 2014, 10, 996–1005, doi:10.3762/bjoc.10.99

• which the benzyl group also was cleaved (NMR evidence). Such a reductive cleavage of the P–C bond from phosphinoyl indoles is a reaction that we are still exploring. A plausible pathway for the formation of phosphinoylindoles 6 and 9–19 is shown in Scheme 6. As depicted above in Scheme 2, the normal

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• ] were one of the earliest examples of folate disulfide–drug conjugates and after the conjugate is internalized by endocytosis, it was demonstrated that the endosomes exert reductive cleavage. For conjugate 7 we found that disulfide cleavage provided a thiol derivative of ansamitocin P-3 (4, AP-3) 8 with

• after reductive cleavage, ansamitocin derivative 8 still showed sufficient antiproliferative activity. This is in line with our observation that structural changes at the aromatic ring do not affect the biological properties of the ansamitocins to a great extent [13][14][15][16][17][18][19][20][21]. In

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

Synthesis, characterization and initial evaluation of 5-nitro-1-(trifluoromethyl)-3H-1λ³,2-benziodaoxol-3-one

• Nico Santschi,
• Roman C. Sarott,
• Elisabeth Otth,
• Reinhard Kissner and
• Antonio Togni

Beilstein J. Org. Chem. 2014, 10, 1–6, doi:10.3762/bjoc.10.1

• -substituted compounds. When comparing the same unit I–X within the analogous compounds 2 and 3, a shorter bond would intuitively correspond to a stronger bond. Therefore, based on simple geometrical parameters, reagent 3 was expected to be slightly less reactive compared to 2, meaning that reductive cleavage

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• is achieved via an asymmetric addition of phenylethylzinc to the imine N-oxide 2.66 yielding the corresponding 3,4-dihydroisoquinoline-N-hydroxide 2.68. Further reductive cleavage of the hydroxylamine moiety followed by activation with 4-nitrophenyl chloroformate [79] yields the intermediate 2.69. In

Polymeric redox-responsive delivery systems bearing ammonium salts cross-linked via disulfides

• Christian Dollendorf,
• Martin Hetzer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 1652–1662, doi:10.3762/bjoc.9.189

• successfully synthesized by cross-linking reactions via quaternary ammonium compounds with the disulfide-bearing cross-linker CL 1. The ability of the polymer network to enclose and release substances by reductive cleavage or oxidative formation of disulfide bonds was shown exemplarily using different dyes

• poly(DEAAm-co-DMAEMA) (right) in distilled water. (b) Reductive cleavage of cross-linked poly(DEAAm-co-DMAEMA) networks containing phenolphthalein in pH 10 buffer solution. Storage modulus G’ as function of applied shear stress τ for samples 4 and 5 containing different amounts of CL 1 or CL 2. Storage

• (empty symbols) and 30% H2O2 (half symbols). Swelling degree Q of polymer discs 4–6 as a function of the amount and type of containing cross-linker. (a) Synthesis of a polycationic cross-linked hydrogel containing disulfide groups. (b) Reductive cleavage and oxidative rebuilding of disulfide groups in