Synthetic Approach Toward Antibiotic Tunicamycins, 4. X-Ray Crystal Structure Analysis of a Higher-Carbon Nitro Sugar

Abstract

A higher-carbon carbohydrate, a derivative of undecose has been synthesized by the potassium fluoride-catalyzed addition of a nitro sugar to a sugar aldehyde. The addition of methyl 5-de-oxy-2,3-O-isopropylidene-5-nitro-β-D-ribofuranoside to methyl 2-benzyloxycarbonylamino-2-deoxy-3,4-O-isopropylidene-α-D-galacto-dialdopyranoside-(1, 5) yielded a single diastereomer of the nitro undecose derivative. The absolute configuration of two chiral centers of the derivative has been established by the X-ray crystal structure analysis.     

Conversion of glucosamine to galactosamine and allosamine derivatives: control of inversions of stereochemistry at C-3 and C-4.

The reactions of sodium benzoate with a series of trimesylates derived from glucosamine have been examined in an attempt to gain facile access to galactosamine analogues. Trimesylate 17, in which the amino group was protected as a phthalimide, underwent double displacement at positions 4 and 6 to give the dibenzoate 18 with the desired galactosamine configuration. In contrast, trimesylates 21 and 27, in which the amino groups were protected as acetamides, unexpectedly underwent double displacement at positions 3 and 6, giving products 22 and 28, respectively, with allosamine configurations.     

Synthetic approaches to thienamycin: Carbon-carbon bond formation at C-4 of azetidin-2-ones

A mild and efficient method of β-lactam alkylation has been achieved using 4-acetoxy-2-azetidinone and a variety of silyl enol ethers.     

Nuclear analogs of β-lactam antibiotics 8. Stereospecific synthesis of a C-3 methoxylated monocyclic s-lactam

Methoxylation of $\text{1}$(R = PhOCH₂CO) occurred stereospecifically from the α-face as determined by x-ray crystallography to provide $\text{2}$ which was converted to $\text{4}$ whose $\text{in}$$\text{vitro}$ antimicrobial activity was determined.     

Stereoselective Functionalization at C-2 and C-3 of the Gibberellin via an Intramolecular Free Radical Cyclization Approach

The gibberellins (GAs) are a group of naturally-occurring tetracyclic diterpenoid plant growth hormones which are widely present in higher plants and some fungal species. To date over one hundred GAs have been identified and found to be involved in almost every aspect and stage of the growth and development of plants1.Among the GAs identified to date, gibberellic acid (GA3) 1 is the most active and widely used naturally occurring gibberellin. However structure-activity relationship studies …     

High-Pressure Approach to the Synthesis of Optically Pure Methyl 4-Deoxyheptosides

Recently we have described¹ high pressure (4+2) cycloaddition of l-methoxybuta-1,3-diene (1)to 2,3-0-isopropylidene-D-glyceraldehyde (z), which gives rise to chiral cycloadducts 3 (Scheme). action was carried out under high-pressure conditions (22 kbar, 50°C. diethyl ether as solvent, 20 h, 80% yield)2 four diastereoisomeric adducts were formed in a ratio of 3a:3b:3c:3d=66:16:13:5. The reaction mixture was separated by column chromatography yielding two fractions which contained diastereoisomeric mixtures (3a+3b) and (3c+3d), respectively. Absolute configuration at the C-5 carbon atom in both mixtures was established by chemical correlation.' These results prompted us to use a mixture (3a+3b), being stereochemically pure at C-5 chiral center, in the synthesis of optically active methyl 4-deoxyheptosides (Scheme).     

Chemoselective functionalization of α-carbolines at the C-2, C-3, C-4, and C-6 positions using Suzuki-Miyaura reactions

The synthesis of 2-, 3-, 4-, and 6-substituted pyrido[2,3-b]indoles (α-carbolines) by palladium-catalyzed cross-coupling reactions from the corresponding halopyrido[2,3-b]indoles is described. A sequential and a one-pot chemoselective double Suzuki-Miyaura coupling route is presented for the synthesis of symmetrically and unsymmetrically disubstituted pyrido[2,3-b]indoles.     

Stereoselective Synthesis of 4a-Methyloctahydrophenanthrenes: A Novel Approach. III. C-9 and C-10 Substituted Series

A general approach to substituted octahydrophenanthrenes was developed, which allows the stereoselective introduction of functionality at all positions. The procedure utilizes 4a-methyl-2,3,4,4a,9, 10-hexahydrophenanthrene 1, readily available from phenanthrene by reductive alkylation.     

Reductive Deoxygenation of Carbonyl to Methylene by LiAlH4／InBr3

The reductive deoxygenation of aldehydes and ketones into the corresponding alkanes is accomplished by LiAlH4 in the presence of Lewis acid InBr3. It provides a convenient method to complete the transformation from carbonyl compounds to alkanes.     

Functionalization at C-5 and at the C-6 methyl group of 4-methoxy-6-methyl-2-pyrone

A new entry to C-5 substituted 4-hydroxy-6-methyl-2-pyrones has been achieved. The best conditions to prepare the monobromo and the dibromo derivatives at C-3 and the C-6 methyl group of the title pyrone have been defined. The synthetic applicability of the phosphonium salts at CH₃-C-6 of both 4-methoxy-6-methyl-2-pyrone, 5 , and dehydroacetic acid, 2 , has also been evaluated.     

Chemistry of pyrones related to dehydroacetic acid. Functionalization at C-5 and at the methyl group at C-6. An attempted synthesis of a thromboxane B2 analogue

New derivatives of dehydroacetic acid and triacetic acid lactone functionalized at both C-5 and at the methyl group at C-6 have been synthesized as intermediates for the preparation of thromboxane B₂ analogues. 6-Mercaptomethyl-4-methoxy-2-pyrone and some derived thioethers have been also prepared. New thioether derivatives of O-alkyloximes of dehydroacetic acid have been synthesized and tested for herbicidal activity.     

Stereospecific addition of nucleophiles to enaminones and the synthesis of myrtine and 4-epimyrtine.

Stereospecific syntheses of the quinolizidine alkaloid myrtine and its 4-epimer are accomplished by 1,-nucleophilic addition to the enaminones $\text{3}$.     

Synthetic Studies on Halichlorine and Pinnaic Acid. Stereospecific Preparation of the Azaspiro Core Structure

Halichlorine and Pinnaic acid are two novel marine natural products isolated from a Japanese sponge, and an Okinawan bivalve respectively. The unique azaspirl[4.5]decane-core structure prexent in both compounds provides a synthetic challenge, Herein, we describe a synthetic approach to the azaspiro[4.5]decane-core structure through an intramolecular[3+2] cycloaddition followed by an intra-molecular Michael addition and in situ isomerization to afford the azaspirocyclic core structures stereospecifically in 10 steps with 40% overall yield. Alternatively, the same core structure was achieved by tandem cycloaddition and isomerization approach.     

An unusual reaction at C-3 of 4-methoxy-6-methyl-2-pyrone

Triacetic acid lactone methyl ether, 4, can be lithiated at C-3 under kinetically controlled conditions. Further reaction with (E)-2-methyl-3-(4-nitrophenyl)propenal results in an unusual condensation at C-3.