Isochroman Derivatives Research Articles

ChemInform Abstract: Regioselective Introduction of a Methoxy Group at the Benzylic Position of Isochroman Derivatives by Cerium(IV) Oxidation in Methanol.

AbstractThe isochromans (III), prepared by cyclization of the arylethanols (I) with paraformaldehyde (II), and the isochromanones (X) and (XIII) are oxidized with ceric ammonium nitrate in methanol (IV) to produce regioselectively the methoxy derivatives (V), (VII), and (XIV), together with some other oxidation products as outlined in the reaction scheme.

Synthesis of C-glycosylarenes by way of internal reactions of benzylated and benzoylated carbohydrate derivatives

“Internal” C-glycosylarenes [ e.g., (2 R,3 S,3a S,9b R)-3,3a,5,9b-tetrahydro-3-methoxy- and -3,7-dimethoxy-2-methoxymethyl-2 H-furo[3,2- c][2]benzopyran] were prepared by intramolecular reactions of 2- O-benzyl derivatives of methyl 3,5-di- O-methyl- d-xylofuranoside ( 2) and their conversion into authentic C-glycosylated aromatic systems was investigated. The auxiliary benzylic linkage could not be cleaved by hydrogenolysis; isochroman derivatives { e.g., (3 S)-3,4-dihydro-3-[(1 R,2 R)-2-hydroxy-1,3-dimethoxypropyl]-5- methoxy-1 H-2-benzopyran} were obtained under these conditions. However, oxidation of the primary benzylic position with ruthenium tetraoxide gave the corresponding lactone {a dihydroisocoumarin derivative, e.g., (2 R,3 S,3a S,9b R)-2,3,3a,9b-tetrahydro-3,7-dimethoxy-2-methoxy-methyl-5 H-furo[3,2- c][2]benzopyran-5- one} which could be opened by saponification, thereby leading to a stereochemically unique C-glycosylbenzoic acid derivative. The same type of lactone was obtained directly from a derivative of 2 bearing a sufficiently reactive benzoyl group at O-2 (3,5-dimethoxybenzoyl); this process provides a useful approach to a heterocyclic system present in a variety of natural products. In related studies, the 2- O-phenyl substituent was found to be much less reactive than the 2- O-benzyl group in intramolecular Friedel-Crafts reactions of 2- O-substituted glycofuranosides. The first examples of successful internal C-arylation in the pyranoid series were achieved from 2- O-(3-methoxybenzyl)- d-mannopyranosides; the resulting “internal C-glycosides” {(2 R,3 S,4 S,4a S,10b S)-2,3,4,4a,6,10b-hexahydro-3,4,8-trimethoxy-2-methoxymethylpyrano [3,2- c][2]benzopyran and 3,4-bis(benzyloxy)-2-benzyloxymethyl-8-methoxy analog} contain a heterocyclic skeleton closely related to that of the natural product bergenin.

ChemInform Abstract: Unusual 1,5‐Hydride Shifts in Lewis Acid Mediated Reactions of Benzylated Sugars. Synthesis of 3‐Alkylisochroman Derivatives.

AbstractTin(IV) chloride mediated reaction of the benzylated sugars (I) and (III) leads to the formation of the isochroman derivatives (II) and (IV) respectively.

ChemInform Abstract: Intramolecular C‐Arylation of 2,3,5‐Tri‐O‐benzyl‐ and 2,3,5‐Tri‐O‐(3‐methylbenzyl)pentofuranose Derivatives.

Abstract Upon treatment with tin(IV) chloride, 1- O -acetyl-2,3,5-tri- O -benzyl- and 1- O -acetyl-2,3,5-tri- O -(3-methylbenzyl)pentofuranose ( d - ribo , l - arabino ) undergo intramolecular Friedel—Crafts alkylation of the aromatic substituent at O-2 to give unusual internal C -glycosyl compounds (isochroman derivatives) in high yield. The final products are also partially debenzylated at O-3 or O-5 (up to 25%) under these conditions. By contrast, the corresponding methyl glycosides are poor substrates for the intramolecular C -arylation reaction, as methyl 2,3,5-tri- O -(3-methylbenzyl)-β- d -ribofuranoside was found to give preponderantly methyl 3,5-di- O -(3-methylbenzyl)-α- d -ribofuranoside ( 11 ) (49%), and the C -arylation product in 30% yield only in the presence of the same Lewis acid. The competitive formation of 11 is thought to be due to the anomerization of the substrate leading to a tin(IV) complex coordinated with O-1 and O-2, which promoted the cleavage of the benzyl group at O-2. These reactions provide a novel and efficient C -arylation method and suggest a new approach to selectively protected d -ribofuranose derivatives. Evidence for the uncommon C -arylated structure of the new products was gained from their 1 H- and 13 C(APT)-n.m.r. spectra.

Intramolecular C-arylation of 2,3,5-tri- O-benzyl- and 2,3,5-tri- O-(3-methylbenzyl)-pentofuranose derivatives

Upon treatment with tin(IV) chloride, 1- O-acetyl-2,3,5-tri- O-benzyl- and 1- O-acetyl-2,3,5-tri- O-(3-methylbenzyl)pentofuranose ( d- ribo, l- arabino) undergo intramolecular Friedel—Crafts alkylation of the aromatic substituent at O-2 to give unusual internal C-glycosyl compounds (isochroman derivatives) in high yield. The final products are also partially debenzylated at O-3 or O-5 (up to 25%) under these conditions. By contrast, the corresponding methyl glycosides are poor substrates for the intramolecular C-arylation reaction, as methyl 2,3,5-tri- O-(3-methylbenzyl)-β- d-ribofuranoside was found to give preponderantly methyl 3,5-di- O-(3-methylbenzyl)-α- d-ribofuranoside ( 11) (49%), and the C-arylation product in 30% yield only in the presence of the same Lewis acid. The competitive formation of 11 is thought to be due to the anomerization of the substrate leading to a tin(IV) complex coordinated with O-1 and O-2, which promoted the cleavage of the benzyl group at O-2. These reactions provide a novel and efficient C-arylation method and suggest a new approach to selectively protected d-ribofuranose derivatives. Evidence for the uncommon C-arylated structure of the new products was gained from their 1H- and 13C(APT)-n.m.r. spectra.

ChemInform Abstract: Synthesis of Carbocyclic Spiro Compounds from Isochroman Derivatives via Intramolecular Aldol Reaction.

AbstractCoupling the 1‐ethoxychroman (I) with the cyclic ketones (II), followed by ring cleavage and oxidation, yields the aldehydes (VI).

Synthesis of Carbocyclic Spiro Compounds from Isochroman Derivatives via Intramolecular Aldol Reaction

Synthesis of Carbocyclic Spiro Compounds from Isochroman Derivatives via Intramolecular Aldol Reaction

ChemInform Abstract: SYNTHESIS AND ANTITUMOR ACTIVITY OF TROPOLONE DERIVATIVES. 2

AbstractEs werden die Verbindungen (II), (IV), (V), (IX) und (XI) synthetisiert und auf Antitumor‐ Wirkung untersucht.

Synthesis and antitumor activity of tropolone derivatives. 2

Structural requirement for antitumor activity of tropolone derivatives 2-4 was explored. Isochroman derivatives (6-17, 20, and 23) and alpha, alpha-disubstituted compounds 26-30 were synthesized and their antitumor activities were tested. These nontroponoid derivatives were all inactive, implying that a tropolone ring is essential for the activity. Several compounds related to the monotropolone analogue 3 were synthesized. Among them, 31-33 showed significant activity, but their potencies were considerably weaker than those of binary tropolone analogues 4.

ChemInform Abstract: REACTIVITY OF ISOCOUMARINS. V. REACTION OF 1‐ETHOXYISOCHROMAN WITH ACTIVE METHYLENE COMPOUNDS

AbstractEthoxyisochroman (I) reagiert mit den methylenaktiven Verbindungen (II) zu den Kondensationsprodukten (III) und (IV).

Reactivity of isocoumarins. V. Reaction of 1-ethoxyisochroman with active methylene compounds.

Active methylene compounds, diethyl malonate, α-tetralone, dimedone, acetyl-acetone, malononitrile, and diketene, were reacted with 1-ethoxyisochroman (1) to give the corresponding 1-substituted isochroman derivatives, 4, 5, 6, 7, 8, 9, 10, and 11, respectively. When 4 was treated with sodium ethoxide or potassium tert-butoxide, ethyl 1, 4-dihydro-2-naphthoate (14a), ethyl 1, 2-dihydro-2-naphthoate (14b), and ethyl 2-naphthoate (13) were obtained. On the other hand, the reaction of 2-(1-isochromanyl) cyclohexanone (3) with potassium tert-butoxide afforded 9-formyl-1, 2, 3, 4-tetrahydroanthracene (20) and 1, 2, 3, 4, 9, 10-hexahydroanthracene (21). The conversion mechanisms of 1-substituted isochromans (2, 3, 4, and 7) into naphthalenes (13, 14a, b, and 18) and 1, 2, 3, 4-tetrahydroanthracenes (20 and 21) are proposed.

Konstitution und absolute Konfiguration der Rhoeadin‐Alkaloide (+)‐Alpinigenin und (+)‐cis‐Alpinigenin

The constitution and absolute configuration of the rhoeadine alkaloids (+)‐alpinigenine and (+)‐cis‐alpinigenine.The fundamental structure of the hemi‐acetal phenylbenzazepine alkaloid (+)‐alpinigenine (1), isolated from Papaver bracteatum LINDL., was derived essentially from 1H‐NMR.‐ and mass‐spectra of 1 and its derivatives 7, 10 and 14 (cf. Scheme 2). The positioning of the four methoxy groups in the two aromatic rings could be deduced from the 1H‐NMR.‐spectra of the N‐oxides 14 and 15 in which, as a result of favourable sterical and conformational behaviour, an interaction exists between the N‐oxide oxygen atom and one of the two ortho protons in ring C.The B/D‐trans‐fused 1 undergoes isomerization in 1N HCl to cis‐alpinigenine (16). A stereochemical correlation between bases in the trans‐and cis‐series was enabled via an Emde degradation of the corresponding methylacetal‐methyliodides 21 resp. 19 leading to the enantiomeric isochroman derivatives 22 resp. 23 which are achiral at C (2) (Scheme 4).The configuration at C (14) in the hemi‐acetals (eg. 1 and 16) and the methyl ethers (eg. 7 and 8) is discussed in detail (cf. Scheme 7). (+)‐Alpinigenine (1) has the (1S, 2R, 14R) configuration and (+)‐cis‐alpinigenine (16), in chloroform or acetone solution, the (1R, 2R, 14R) configuration.

Studies on 3,4-fused 5,6-dihydro-2h-pyran derivatives. I. A new synthetic method of dihydrofuropyran derivative and 1-substituted isochroman derivatives (author's transl)

Studies on 3,4-fused 5,6-dihydro-2h-pyran derivatives. I. A new synthetic method of dihydrofuropyran derivative and 1-substituted isochroman derivatives (author's transl)

Formation of some isochromene derivatives by reaction of veratyl ketones and veratric acid with benzoin

Formation of some isochromene derivatives by reaction of veratyl ketones and veratric acid with benzoin