Two Halogenated Sesquiterpenoids from the Fruits of Alpinia oxyphylla

Two new halogenated eremophilane‐type sesquiterpenoids, (11S)‐ and (11R)‐12‐chloronootkaton‐11‐ol ( 1 and 2 , resp.), together with five known sesquiterpenoids, nootkatone ( 3 ), 7‐epiteucrenone B ( 4 ), oxyphyllenodiol A ( 5 ), oxyphyllenodiol B ( 6 ), and alpinenone ( 7 ), were isolated from the EtOH extract of the fruits of Alpinia oxyphylla Miq . The structures were elucidated based on the analyses of their spectroscopic data.     

华泽兰的七个新的倍半萜

Seven new sesquiterpenoids, namely eupatochinilides Ⅰ-Ⅶ （1-7）, together with eight known compounds, euponin （8）, mollisorin A （9）, niveusin B （10）, 8β-（4＇-acetoxy-tiglyloxy）-3β-hydroxy-6Hβ,7Hα-germacra-1（10）E,4E,11（13）-trien-6,12-olide （11）, eupalinifide B （12）, 8β-（4＇-hydroxytigloyloxy）-5-desoxy-8-desacyleuparotin （13）, 3-deacetyeupalinin A （14）, and 15-hydroxyleptocarpin （15）, were isolated from the ethanolic extract of the whole plant of Eupatorium chinense L. Their structures and stereochemistry were established by spectroscopic methods and GIAO based ^13C NMR chemical shift calculations.     

Characterization of Eight New Secondary Metabolites from the Mutant Strain G‐444 of Tubercularia sp. TF5

Eight new metabolites, including five new sesquiterpenoids, 10,11‐epoxyguaian‐10‐ol ( 1 ), 10,11‐epoxyguaian‐13‐ol ( 2 ), a new backbone sesquiterpene rearranged from guaiane ( 3 ), two 1,5 : 1,10‐disecoguaianes, 4 and 5 , two new dihydroisocoumarins, 7‐chloromellein‐4‐ol ( 6 ) and 7‐chloromellein‐5‐ol ( 7 ), and one new tetralone, 7‐chloroscytalone ( 8 ), were isolated from the mutant strain G‐444 of Tubercularia sp. TF5, an endophytic fungus of Taxus mairei, along with ten known compounds, 3,4‐dihydro‐4,8‐dihydroxy‐2H‐naphthalen‐1‐one ( 9 ), (3R,4S)‐4‐hydroxymellein ( 10 ), 5‐formylmellein ( 11 ), 5‐carboxymellein ( 12 ), sporogen‐AO1 ( 13 ), tuberculariols A ( 14 ) and B ( 15 ), hymatoxin E ( 16 ), 4‐oxo‐4H‐pyran‐3‐acetic acid ( 17 ), and penicillic acid ( 18 ). Their structures were elucidated by spectroscopic analyses including HR‐ESI‐MS, 1D‐ and 2D‐NMR (HMQC, HMBC, ¹H,¹H‐COSY and NOESY). The antimicrobial activities of 1 – 8 were evaluated, but none showed any substantial effect.     

7‐Halogenated 7‐Deazapurine 2′‐Deoxyribonucleosides Related to 2′‐Deoxyadenosine, 2′‐Deoxyxanthosine,and 2′‐Deoxyisoguanosine: Syntheses and Properties

A series of 7‐fluorinated 7‐deazapurine 2′‐deoxyribonucleosides related to 2′‐deoxyadenosine, 2′‐deoxyxanthosine, and 2′‐deoxyisoguanosine as well as intermediates 4b – 7b, 8, 9b, 10b , and 17b were synthesized. The 7‐fluoro substituent was introduced in 2,6‐dichloro‐7‐deaza‐9H‐purine ( 11a ) with Selectfluor (Scheme 1). Apart from 2,6‐dichloro‐7‐fluoro‐7‐deaza‐9H‐purine ( 11b ), the 7‐chloro compound 11c was formed as by‐product. The mixture 11b / 11c was used for the glycosylation reaction; the separation of the 7‐fluoro from the 7‐chloro compound was performed on the level of the unprotected nucleosides. Other halogen substituents were introduced with N‐halogenosuccinimides ( 11a → 11c – 11e ). Nucleobase‐anion glycosylation afforded the nucleoside intermediates 13a – 13e (Scheme 2). The 7‐fluoro‐ and the 7‐chloro‐7‐deaza‐2′‐deoxyxanthosines, 5b and 5c , respectively, were obtained from the corresponding MeO compounds 17b and 17c , or 18 (Scheme 6). The 2′‐deoxyisoguanosine derivative 4b was prepared from 2‐chloro‐7‐fluoro‐7‐deaza‐2′‐deoxyadenosine 6b via a photochemically induced nucleophilic displacement reaction (Scheme 5). The pK_a values of the halogenated nucleosides were determined (Table 3). ¹³C‐NMR Chemical‐shift dependencies of C(7), C(5), and C(8) were related to the electronegativity of the 7‐halogen substituents (Fig. 3). In aqueous solution, 7‐halogenated 2′‐deoxyribonucleosides show an approximately 70% S population (Fig. 2 and Table 1).     

Stereoselective Preparation of 3‐Amino‐2‐fluoro Carboxylic Acid Derivatives,and Their Incorporation in Tetrahydropyrimidin‐4(1H)‐ones,and in Open‐Chain and Cyclic β‐Peptides

The preparation of (2S,3S)‐ and (2R,3S)‐2‐fluoro and of (3S)‐2,2‐difluoro‐3‐amino carboxylic acid derivatives, 1 – 3 , from alanine, valine, leucine, threonine, and β³h‐alanine (Schemes 1 and 2, Table) is described. The stereochemical course of (diethylamino)sulfur trifluoride (DAST) reactions with N,N‐dibenzyl‐2‐amino‐3‐hydroxy and 3‐amino‐2‐hydroxy carboxylic acid esters is discussed (Fig. 1). The fluoro‐β‐amino acid residues have been incorporated into pyrimidinones ( 11 – 13 ; Fig. 2) and into cyclic β‐tri‐ and β‐tetrapeptides 17 – 19 and 21 – 23 (Scheme 3) with rigid skeletons, so that reliable structural data (bond lengths, bond angles, and Karplus parameters) can be obtained. β‐Hexapeptides Boc[(2S)‐β³hXaa(αF)]₆OBn and Boc[β³hXaa(α,αF₂)]₆‐OBn, 24 – 26 , with the side chains of Ala, Val, and Leu, have been synthesized (Scheme 4), and their CD spectra (Fig. 3) are discussed. Most compounds and many intermediates are fully characterized by IR‐ and ¹H‐, ¹³C‐ and ¹⁹F‐NMR spectroscopy, by MS spectrometry, and by elemental analyses, [α]_D and melting‐point values.     

Sesquiterpenoids and 2‐(2‐Phenylethyl)‐4H‐chromen‐4‐one (=2‐(2‐Phenylethyl)‐4H‐1‐benzopyran‐4‐one) Derivatives from Aquilaria malaccensis Agarwood

The four new sesquiterpenoids 1 – 4 , and the new 2‐(2‐phenylethyl)‐4H‐chromen‐4‐one (=2‐(2‐phenylethyl)‐4H‐1‐benzopyran‐4‐one) derivative 5 , together with the two known sesquiterpenoids 6 and 7 , the five known chromenones 8 – 12 , and 1‐hydroxy‐1,5‐diphenylpentan‐3‐one ( 13 ), were isolated from a 70% MeOH extract of Aquilaria malaccensis agarwood chips. Their structures were elucidated on the basis of comprehensive spectral analyses and comparison with literature data.     

Two New Diterpenoids from Callicarpa pedunculata

Two new diterpenoids, pedunculatic acid A (= (4R,5α,7α)‐7‐ethoxy‐9β,13β‐dioxyabiet‐8(14)‐en‐18‐oic acid; 1 ) and pedunculatic acid B (= (4S,5α,12β)‐8β,14β‐epoxy‐12‐hydroxy‐11‐oxototaran‐19‐oic acid; 2 ), together with three known sesquiterpenoids, were isolated from the Chinese medicinal herb Callicarpa pedunculata R. Brown . Their structures were elucidated by spectroscopic analyses, including 1D‐ and 2D‐NMR, and by high‐resolution mass spectrometry.     

Stereoselective Synthesis of [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐D‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐L‐valine]cyclosporin A

Addition of various amines to the 3,3‐bis(trifluoromethyl)acrylamides 10a and 10b gave the tripeptides 11a – 11f , mostly as mixtures of epimers (Scheme 3). The crystalline tripeptide 11f ₂ was found to be the N‐terminal (2‐hydroxyethoxy)‐substituted (R,S,S)‐ester HOCH₂CH₂O‐D ‐Val(F₆)‐MeLeu‐Ala‐O^tBu by X‐ray crystallography. The C‐terminal‐protected tripeptide 11f ₂ was condensed with the N‐terminus octapeptide 2b to the depsipeptide 12a which was thermally rearranged to the undecapeptide 13a (Scheme 4). The condensation of the epimeric tripeptide 11f ₁ with the octapeptide 2b gave the undecapeptide 13b directly. The undecapeptides 13a and 13b were fully deprotected and cyclized to the [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐D ‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐L ‐valine]]cyclosporins 14a and 14b , respectively (Scheme 5). Rate differences observed for the thermal rearrangements of 12a to 13a and of 12b to 13b are discussed.     

Unusual Guaiane Sesquiterpenoids from Artemisia rupestris

Two new guaiane sesquiterpenoids, (1β,5β)‐1‐hydroxyguaia‐4(15),11(13)‐dieno‐12,5‐lactone ( 1 ) and 1,5‐epoxy‐4‐hydroxyguai‐11(13)‐en‐12‐oic acid ( 2 ), together with five known compounds, rupestonic acid ( 3 ), strobilactone A ( 4 ), antiquorin ( 5 ), isosclerone ( 6 ), and 5‐hydroxy‐2′,3′,4′,7,8‐pentamethoxyflavone ( 7 ), were isolated from a 95% EtOH extract of Artemisia rupestris. Compounds 1 and 2 are rare examples of guaiane sesquiterpenoids, incorporating a 12,5‐lactone group or featuring a 1,5‐epoxy ring, respectively. The structures of 1 and 2 were identified by various spectroscopic methods. Compounds 1, 4 , and 5 exhibited moderate cytotoxic activities against the human lung cancer 95‐D cell line with IC₅₀ values of 11.3, 19.8, and 34.5 μM , respectively.     

Terpenoids from Two Dicranopteris Species

Two new compounds, (6S,13S)‐6‐{[β‐D ‐glucopyranosyl‐(1→4)‐α‐L ‐rhamnopyranosyl]oxy}cleroda‐3,14‐dien‐13‐ol ( 1 ) and kadsuric acid 3‐methyl ester ( 2 ), together with nine known compounds, (6S,13E)‐6‐{[β‐D ‐glucopyranosyl‐(1→4)‐α‐L ‐rhamnopyranosyl]oxy}cleroda‐3,13‐dien‐15‐ol ( 3 ), (6S,13S)‐6‐[6‐O‐acetyl‐β‐D ‐glucopyranosyl‐(1→4)‐α‐L ‐rhamnopyranosyl]oxy}‐13‐{[α‐L ‐rhamnopyranosyl‐(1→4)‐β‐D ‐fucopyranosyl]oxy}cleroda‐3,14‐diene ( 4 ), (6S,13S)‐6‐{[6‐O‐β‐D ‐glucopyranosyl‐(1→4)‐α‐L ‐rhamnopyranosyl]oxy}‐13‐{[α‐L ‐rhamnopyranosyl‐(1→4)‐β‐D ‐fucopyranosyl]oxy}cleroda‐3,14‐diene ( 5 ), 15‐hydroxydehydroabietic acid ( 6 ), 15‐hydroxylabd‐8(17)‐en‐19‐oic acid ( 7 ), junicedric acid ( 8 ), (4β)‐kaur‐16‐en‐18‐oic acid ( 9 ), (4β)‐16‐hydroxykauran‐18‐oic acid ( 10 ), and (4β,16β)‐16‐hydroxykauran‐18‐oic acid ( 11 ) were isolated from the fronds of Dicranopteris linearis or D. ampla. Their structures were established by extensive 1D‐ and 2D‐NMR spectroscopy. Compounds 1 and 3 – 8 showed no anti‐HIV activities.     

Synthesis of A/B Ring Analogs of Territrem B and Evaluation of Their Biological Activities

Two series of territrem B analogs, i.e., 5 – 10 , containing both the 2‐en‐1‐one‐A‐ring and the aromatic‐E‐ring pharmacophores were designed and synthesized from jujubogenin ( 4a ). The anti‐acetylcholinesterase (anti‐AChE), anti‐caspase‐3, and other biological activities of these territrem‐B analogs and their intermediates were assessed. Compound 9b, 22a , and 24f were shown to be weak inhibitors of AChE. None of the synthesized compounds exhibited significant inhibitory activity on caspase‐3. On the other hand, compounds 22e, 24a, 7b , and 8a showed mild cytotoxicity on cultured KB cells, with IC₅₀ values of 2.0, 3.5, 6.5, and 14 μM , respectively. In addition, compounds 23b and 5f were active against injury arising from oxygen‐glucose deprivation.     

Nine New Sesquiterpenes from Dendrobium nobile

Nine new sesquiterpenes, i.e., dendronobilins A–I ( 1 – 9 ), with copacamphane‐type ( 1 ), picrotoxane‐type ( 2 – 6 ), muurolene‐type ( 7 ), alloaromadendrane‐type ( 8 ), and cyclocopacamphane‐type ( 9 ) skeletons, were isolated from the 60% EtOH extract of the stems of Dendrobium nobile. Their structures were established as (1R,2R,4S,5S,6S,8S,9R)‐2,8‐dihydroxycopacamphan‐15‐one ( 1 ), (2β,3β,4β,5β)‐2,4,11‐trihydroxypicrotoxano‐3(15)‐lactone ( 2 ), (2β,3β,5β,9α,11β)‐2,11‐epoxy‐9,11,13‐trihydroxypicrotoxano‐3(15)‐lactone ( 3 ), (2β,3β,5β,12R*)‐2,11,13‐trihydroxypicrotoxano‐3(15)‐lactone ( 4 ), (2β,3β,5β,12S*)‐2,11,13‐trihydroxypicrotoxano‐3(15)‐lactone ( 5 ), (2β,3β,5β,9α)‐9,10‐cyclo‐2,11,13‐trihydroxypicrotoxano‐3(15)‐lactone ( 6 ), (9β,10α)‐muurol‐4‐ene‐9,10,11‐triol ( 7 ), (10α)‐alloaromadendrane‐10,12,14‐triol ( 8 ), and (5β)‐cyclocopacamphane‐5,12,15‐triol ( 9 ) on the basis of spectroscopic analysis. The absolute configuration of compound 1 was tentatively assigned as (1R,2R,4S,5S,6S,8S,9R) according to its CD spectrum and the octant rule. Compounds 1 and 4 – 9 were inactive in our preliminary in vitro immunomodulatory bioassay.     

Synthesis and Structural Characterization of Metal Complexes of 2‐Formylpyrrole‐4N‐ethylthiosemicarbazone (4 EL1) and 2‐Acetylpyrrole‐4N‐ethylthiosemicarbazone (4 EL2)

The reactions of ⁴N‐ethyl‐2‐[1‐(pyrrol‐2‐yl)methylidene(hydrazine carbothioamide ( 4 EL₁ ) and ⁴N‐ethyl‐2[1‐(pyrrol‐2‐yl)ethylidene(hydrazine carbothioamide ( 4 EL₂ ) with Group 12 metal halides afforded complexes of types [M(L)₂X₂] (M = Zn, Cd; L = 4 EL₁, 4 EL₂; X = Cl, Br, I; 1 – 6 , 14 – 19 ) and [M(L)X₂] (M = Hg; L = 4 EL₁, 4 EL₂; X = Cl, Br, I; 7 – 9 , 20 – 22 ). In addition, reaction of 4 EL₁ with salts of Cu^II, Ni^II, Pd^II and Pt^II afforded compounds of type [M(4 EL₁–H)₂] ( 10 – 13 ). The new compounds were characterized by elemental analysis, FAB mass spectrometry, IR and electronic spectroscopy and, for sufficiently soluble compounds, ¹H, ¹³C and, when appropriate, ¹¹³Cd or ¹⁹⁹Hg NMR spectrometry. The spectral data suggest that in their complexes with Group 12 metal cations, both thiosemicarbazones are neutral and S‐monodentate; and for [Zn(4 EL₁)₂I₂] ( 3 ), [Cd(4 EL₁)₂Br₂] ( 5 ) and [Hg(4 EL₁)Cl₂]₂ ( 7 ) this was confirmed by X‐ray diffractometry. By contrast, in its complexes with Cu^II and Group 10 metal cations, 4 EL₁ is monodeprotonated and S,N‐bidentate, as was confirmed by X‐ray diffractometry for [Ni(4 EL₁–H)₂] ( 11 ) and [Pd(4 EL₁–H)₂] ( 12 ).     

Two New Eremophilane‐Type Sesquiterpenoids from the Rhizomes of Ligularia veitchiana (Hemsl.) Greenm

Two new eremophilane‐type sesquiterpenoids eremophil‐6‐en‐11‐ol ( 1 ) and (7α,9α,10α)‐9,10‐epoxy‐eremophilan‐11‐ol ( 2 ), together with a known eremophilane‐type (6α,8α)‐6,8‐dihydroxyeremophil‐7(11)‐en‐12‐oic acid 12,8‐lactone ( 3 ) were isolated from the rhizomes of Ligularia veitchiana. The structures of 1 and 2 were established by spectral analysis including ¹H‐ and ¹³C‐NMR, HSQC, HMBC, and HR‐ESI‐MS data. The compounds 1 and 3 were assessed against lung‐cancer (A549) and stomach‐cancer (BCG823) cell lines by the MTT method. The results showed that 1 exhibited significant inhibiting activities on the growth of these cancer cells with IC₅₀ values between 1–100 μg/ml, whereas compound 3 had no effect on the same cell lines.     

Reactions of Di(tert‐butyl)diazomethane with Acceptor‐Substituted Ethylenes

Di(tert‐butyl)diazomethane ( 4 ) is a nucleophilic 1,3‐dipole with strong steric hindrance at one terminus. In its reaction with 2,3‐bis(trifluoromethyl)fumaronitrile ((E)‐ BTE ), a highly electrophilic tetra‐acceptor‐substituted ethene, an imino‐substituted cyclopentene 9 is formed as a 1 : 2 product. The open‐chain zwitterion 10 , assumed as intermediate, adds the second molecule of (E)‐ BTE . The ¹⁹F‐ and ¹³C‐NMR spectra allow the structural assignment of two diastereoisomers, 9A and 9B . The zwitterion 10 can also be intercepted by dimethyl 2,3‐dicyanofumarate ( 11 ) and furnishes diastereoisomeric cyclopentenes 12A and 12B ; an X‐ray‐analysis of 12B confirms the ‘mixed’ 1 : 1 : 1 product. Competing is an (E)‐ BTE ‐catalyzed decomposition of 4 to give 2,3,4,4‐tetramethylpent‐1‐ene ( 7 )+N₂; the reaction of (E)‐ BTE with a trace of water appears to be responsible for the chain initiation. The H₂SO₄‐catalyzed decomposition of diazoalkane 4 , indeed, produced the alkene 7 in high yield. The attack on the hindered diazoalkane 4 by 11 is slower than that by (E)‐ BTE ; the zwitterionic intermediate 21 undergoes cyclization and furnishes the tetrasubstituted furan 22 . In fumaronitrile, electrophilicity and steric demand are diminished, and a 1,3‐cycloaddition produces the 4,5‐dihydro‐1H‐pyrazole derivative 25 . The reaction of 4 with dimethyl acetylenedicarboxylate leads to pyrazole 29 +isobutene.     

Synthesis and Anti‐tumor Evaluation of B‐ring Modified Caged Xanthone Analogues of Gambogic Acid

Gambogic acid (GA, 1 ), the most prominent member of Garcinia natural products, has been reported to be a promising anti‐tumor agent. Previous studies have suggested that the planar B ring and the unique 4‐oxa‐tricyclo[4.3.1.0^3,7]dec‐2‐one caged motif were essential for anti‐tumor activity. To further explore the structure‐activity relationship (SAR) of caged Garcinia xanthones, two new series of B‐ring modified caged GA analogues 13a – 13e and 15a – 15e were synthesized utilizing a Claisen/Diel‐Alder cascade reaction. Subsequently, these compounds were evaluated for their in vitro anti‐tumor activities against A549, MCF‐7, SMMC‐7721 and BGC‐823 cancer cell lines by MTT assay. Among them, 13b – 13e exhibited micromolar inhibition against several cancer cell lines, being approximately 2–4 fold less potent in comparison to GA. SAR analysis revealed that the peripheral gem‐dimethyl groups are essential for maintaining anti‐tumor activity and substituent group on C1 position of B‐ring has a significant effect on potency, while modifications at C‐2, C‐3 and C‐4 positions are relatively tolerated. These findings will enhance our understanding of the SAR of Garcinia xanthones and lead to the development of simplified analogues as potential anti‐tumor agents.     

Neutral Penta‐ and Hexacoordinate Silicon(IV) Complexes Containing Two Bidentate Ligands Derived from the α‐Amino Acids (S)‐Alanine, (S)‐Phenylalanine,and (S)‐tert‐Leucine

The neutral hexacoordinate silicon(IV) complex 6 (SiO₂N₄ skeleton) and the neutral pentacoordinate silicon(IV) complexes 7 – 11 (SiO₂N₂C skeletons) were synthesized from Si(NCO)₄ and RSi(NCO)₃ (R=Me, Ph), respectively. The compounds were structurally characterized by solid‐state NMR spectroscopy ( 6 – 11 ), solution NMR spectroscopy ( 6 and 10 ), and single‐crystal X‐ray diffraction ( 8 and 11 were studied as the solvates 8? CH₃CN and 11? C₅H₁₂ ? 0.5 CH₃CN, respectively). The silicon(IV) complexes 6 (octahedral Si‐coordination polyhedron) and 7 – 11 (trigonal‐bipyramidal Si‐coordination polyhedra) each contain two bidentate ligands derived from an α‐amino acid: (S)‐alanine, (S)‐phenylalanine, or (S)‐tert‐leucine. The deprotonated amino acids act as monoanionic ( 6 ) or as mono‐ and dianionic ligands ( 7 – 11 ). The experimental investigations were complemented by computational studies of the stereoisomers of 6 and 7 .     

New Eremophilane Sesquiterpenes from a Rhizome Extract of Petasites hybridus

A total of 21 natural products, 1 – 21 , were isolated from a supercritical CO₂ extract of the rhizomes of Petasites hybridus. Thereby, seven new eremophilane (= (1S,4aR,7R,8aR)‐decahydro‐1,8a‐dimethyl‐7‐(1‐methylethyl)naphthalene) sesquiterpenes, compounds 4, 5, 9, 11, 12, 15 , and 17 , were identified. The new constituent 9‐hydroxyisobakkenolide ( 15 ) is the first representative of a group of compounds closely related to the well‐known, but rare, bakkenolides. Tsoongianolide B ( 18 ) and its degradation product ligularenolide ( 19 ) were found as new Petasites constituents as well. The known eremophilanolide 2 was isolated from a plant source for the first time and the oxofuranopetasin 16 was isolated for the first time from the rhizomes of P. hybridus, together with eight other known compounds. The C(8)‐epimeric 2‐[(tigloyl)oxy]eremophilanolides 3 and 8 could clearly be differentiated. All structures were established by extensive 1D‐ and 2D‐NMR experiments (Tables 1–3), and confirmed by in‐depth GC/MS and HPLC/MS experiments.     

Diastereoisomeric ent‐Labdane Diterpenoids from Andrographis paniculata

Four C(8),C(12)‐diastereoisomers, (8S,12S)‐isoandrographolide ( 1 ), (8S,12R)‐isoandrographolide ( 2 ), (8R,12R)‐isoandrographolide ( 3 ), and (8R,12S)‐isoandrographolide ( 4 ) were isolated from the aerial parts of Andrographis paniculata. The structures of the new compounds 1 – 3 were established on the basis of the spectroscopic data including UV, IR, NMR, HR‐ESI‐MS, and X‐ray diffraction analysis.     

Pteridines. Part CXVII

A series of side chain reactions starting from the 6‐ and 7‐styryl‐substituted 1,3‐dimethyllumazines 1 and 21 as well as from the 6‐ and 7‐[2‐(methoxycarbonyl)ethenyl]‐substituted 1,3‐dimethyllumazine 2 and 22 were performed first by addition of Br₂ to the C?C bond forming the 1′,2′‐dibromo derivatives 3, 4, 24 , and 26 in high yields (Schemes 1 and 3) (lumazine=pteridine‐2,4(1H,3H)‐dione). Treatment of 3 with various nucleophiles gave rise to an unexpected tele‐substitution in 7‐position and elimination of the Br‐atoms generating 7‐alkoxy‐ (see 5 and 6 ), 7‐hydroxy‐ (see 7 ) and 7‐amino‐6‐styryl‐1,3‐dimethyllumazines (see 8 – 11 ) (Scheme 1). On the other hand, 4 underwent, with dilute DBU (1,8‐diazabicyclo[5.4.0]undec‐2‐ene), a normal HBr elimination in the side chain leading to 18 , whereas treatment with MeONa afforded a more severe structural change to 19 . Similarly, 24 and 26 reacted to 27, 32 , and 33 under mild conditions, whereas in boiling NaOMe/MeOH, 24 gave 7‐(2‐dimethoxy‐2‐phenylethyl)‐1,3‐dimethyllumazine ( 30 ) which was hydrolyzed to give 31 (Scheme 3). From the reactions of 4 and 24 with DBU resulted the dark violet substance 20 and 25 , respectively, in which DBU was added to the side chain (Scheme 2). The styryl derivatives 1 and 21 could be converted, by a Sharpless dihydroxylation reaction, into the corresponding stereoisomeric 6‐ and 7‐(1,2‐dihydroxy‐2‐phenylethyl)‐1,3‐dimethyllumazines 34 – 37 (Scheme 4). The dihydroxy compounds 34 and 35 were also acetylated to 38 and 39 which, on catalytic reduction followed by formylation, yielded the diastereoisomer mixtures 40 and 41 . Deacetylation to 42 and 45 allowed the chromatographic separation of the diastereoisomers resulting in the isolation of 43 and 44 as well as 46 and 47 , respectively. Introduction of a 6‐ or 7‐ethynyl side chains proceeded well by a Sonogashira reaction with 6‐ ( 48 ) or 7‐chloro‐1,3‐dimethyllumazine ( 55 ) yielding 49 – 51 and 56 – 58 (Scheme 5). The direction of H₂O addition to the triple bond is depending on the substituents since the 6‐ ( 49 ) and 7‐(phenylethynyl)‐1,3‐dimethyllumazine ( 56 ) showed attack at the 2′‐position yielding 53 and 60 , in contrast to the 6‐ ( 51 ) and 7‐ethynyl‐1,3‐dimethyllumazine ( 58 ) favoring attack at C(1′) and formation of 6‐ ( 52 ) and 7‐acetyl‐1,3‐dimethyllumazine ( 59 ).