Total Syntheses and Biological Evaluation of the Ganoderma lucidum Alkaloids Lucidimines B and C

Although a range of pharmacologically active compounds has been obtained from the mycelium and fruiting bodies of Ganoderma lucidum, the biological properties of the alkaloids present in this functional food remain unknown. Herein, we report total syntheses of lucidimines B and C, key members of the first family of alkaloids isolated from G. lucidum, and the evaluation of these synthetically derived materials as antioxidants and antiproliferative agents. Lucidimine B proved to be a better antioxidant than congener C. Similarly, lucidimine B exhibited antiproliferative properties toward MCF-7 cells (an EC₅₀ value of 0.27 ± 0.02 μmol/mL), whereas lucidimine C was inactive. The former alkaloid arrested the MCF-7 cell cycle in the S phase by inducing DNA fragmentation, hence reducing the mitochondrial membrane potential. This work thus demonstrates, for the first time, that the alkaloidal constituents derived from G. lucidum are biologically active and may, therefore, contribute to the beneficial health claims made for this nutraceutical

Chemoenzymatic Synthesis of the Enantiomer of 4,12-Dihydroxysterpurene, the Structure Assigned to a Metabolite Isolated from the Culture Broth of <i>Stereum purpureum</i>

Compound <i>ent</i>-<b>1</b> has been prepared by engaging a derivative of the enantiomerically enriched and microbially derived <i>cis</i>-1,2-dihydrocatechol <b>6</b> in an intramolecular Diels–Alder reaction, elaboration of the adduct so-formed to the cyclopentannulated bicyclo[2.2.2]­octenone <b>3</b>, and photochemical rearrangement of this to the cyclobutanone <b>2</b>. By such means it has been established that 4,12-dihydroxysterpurene (<b>1</b>) is not the structure of the natural product isolated by Xie and co-workers from a culture broth of <i>Stereum purpureum</i>

Chemoenzymatic Total Syntheses of Ribisins A, B, and D, Polyoxygenated Benzofuran Derivatives Displaying NGF-Potentiating Properties

Total syntheses of the structures, <b>1</b>, <b>2</b>, and <b>4</b>, assigned to the biologically active natural products ribisins A, B, and D, respectively, have been achieved using the microbially derived and enantiomerically pure <i>cis</i>-1,2-dihydrocatechol <b>5</b> as starting material. Key steps include Suzuki–Miyaura cross-coupling, intramolecular Mitsunobu, and tandem epoxidation/rearrangement reactions. As a result of these studies, the structures of ribisins A and D have been confirmed while that of congener B was shown to be represented by <b>31</b> rather than <b>2</b>

Total Synthesis of (±)-Crinane from 6,6-Dibromobicyclo[3.1.0]hexane Using a 5-<i>exo</i>-<i>trig</i> Radical Cyclization Reaction to Assemble the C3a-Arylated Perhydroindole Substructure

Crinane embodies the tetracyclic framework associated with some of the most common Amaryllidaceae alkaloids. It has now been prepared in 10 steps from 6,6-dibromobicyclo[3.1.0]­hexane (<b>2</b>). The initial step involves the thermally induced electrocyclic ring opening of cyclopropane <b>3</b> and capture of the resulting π-allyl cation with benzylamine to give an allylic amine that is readily elaborated to the 3°-amine <b>10</b>. This last compound was engaged in a 5-<i>exo</i>-<i>trig</i> free radical cyclization reaction to give the C3a-arylated perhydroindole <b>11</b>. Compound <b>11</b> was then converted, over two steps, into (±)-crinane, the hydrochloride salt of which has been subjected to single-crystal X-ray analysis

Total Synthesis of (±)-Crinane from 6,6-Dibromobicyclo[3.1.0]hexane Using a 5-<i>exo</i>-<i>trig</i> Radical Cyclization Reaction to Assemble the C3a-Arylated Perhydroindole Substructure

Crinane embodies the tetracyclic framework associated with some of the most common Amaryllidaceae alkaloids. It has now been prepared in 10 steps from 6,6-dibromobicyclo[3.1.0]­hexane (<b>2</b>). The initial step involves the thermally induced electrocyclic ring opening of cyclopropane <b>3</b> and capture of the resulting π-allyl cation with benzylamine to give an allylic amine that is readily elaborated to the 3°-amine <b>10</b>. This last compound was engaged in a 5-<i>exo</i>-<i>trig</i> free radical cyclization reaction to give the C3a-arylated perhydroindole <b>11</b>. Compound <b>11</b> was then converted, over two steps, into (±)-crinane, the hydrochloride salt of which has been subjected to single-crystal X-ray analysis

Syntheses of Gibberellins A₁₅ and A₂₄, the Key Metabolites in Gibberellin Biosynthesis

Gibberellins (GAs) are essential phytohormones involved in numerous aspects of plant growth and development. Notably, the biochemistry and genetics of GA biosynthesis, which is associated with their endogenous regulation, have been largely resolved; however, a crucial unsolved question remains: the precise mechanism of the stepwise oxidation and subsequent removal of C-20 from C₂₀ precursors, leading to bioactive C₁₉ gibberellins, is still unresolved. To satisfy numerous requests from biologists, practical preparations of certain GAs that were isolated in miniscule quantities are highly demanded. Herein, we report the first practical syntheses of GA₁₅ and GA₂₄, the key C₂₀ metabolites in gibberellin biosynthesis, from commercially available GA₃. The protocols are robust and offer the capacity to produce GA₂₄ and GA₁₅ under gram scales in high overall yields and thus aid in further biological and related studies

Chemoenzymatic Total Synthesis and Reassignment of the Absolute Configuration of Ribisin C

The enantiomerically pure and enzymatically derived <i>cis</i>-1,2-dihydrocatechol <b>5</b> has been converted, by two related pathways, into compounds <b>3</b> and <i>ent</i>-<b>3</b>. As a result, it has been determined that the true structure of the natural product ribisin C is represented by <i>ent</i>-<b>3</b>

Vacuolar-Iron-Transporter1-Like Proteins Mediate Iron Homeostasis in Arabidopsis

<div><p>Iron deficiency is a nutritional problem in plants and reduces crop productivity, quality and yield. With the goal of improving the iron (Fe) storage properties of plants, we have investigated the function of three Arabidopsis proteins with homology to <u>V</u>acuolar <u>I</u>ron <u>T</u>ransporter1 (AtVIT1). Heterologous expression of <i><u>V</u>acuolar Iron <u>T</u>ransporter-<u>L</u>ike1</i> (<i>AtVTL1</i>; At1g21140), <i>AtVTL2</i> (At1g76800) or <i>AtVTL5</i> (At3g25190) in the yeast vacuolar Fe transport mutant, <i>Δccc1</i>, restored growth in the presence of 4 mM Fe. Isolated vacuoles from yeast expressing either of the <i>VTL</i> genes in the <i>Δccc1</i> background had a three- to four-fold increase in Fe concentration compared to vacuoles isolated from the untransformed mutant. Transiently expressed GFP-tagged AtVTL1 was localized exclusively and AtVTL2 was localized primarily to the vacuolar membrane of onion epidermis cells. Seedling root growth of the Arabidopsis <i>nramp3/nramp4</i> and <i>vit1-1</i> mutants was decreased compared to the wild type when seedlings were grown under Fe deficiency. When expressed under the 35S promoter in the <i>nramp3/nramp4</i> or <i>vit1-1</i> backgrounds, <i>AtVTL1</i>, <i>AtVTL2</i> or <i>AtVTL5</i> restored root growth in both mutants. The seed Fe concentration in the <i>nramp3/nramp4</i> mutant overexpressing <i>AtVTL1</i>, <i>AtVTL2</i> or <i>AtVTL5</i> was between 50 and 60% higher than in non-transformed double mutants or wild-type plants. We conclude that the VTL proteins catalyze Fe transport into vacuoles and thus contribute to the regulation of Fe homeostasis <i>in planta</i>.</p></div

Chemoenzymatic Total Synthesis and Reassignment of the Absolute Configuration of Ribisin C

The enantiomerically pure and enzymatically derived <i>cis</i>-1,2-dihydrocatechol <b>5</b> has been converted, by two related pathways, into compounds <b>3</b> and <i>ent</i>-<b>3</b>. As a result, it has been determined that the true structure of the natural product ribisin C is represented by <i>ent</i>-<b>3</b>

Chemoenzymatic Total Synthesis and Reassignment of the Absolute Configuration of Ribisin C

The enantiomerically pure and enzymatically derived <i>cis</i>-1,2-dihydrocatechol <b>5</b> has been converted, by two related pathways, into compounds <b>3</b> and <i>ent</i>-<b>3</b>. As a result, it has been determined that the true structure of the natural product ribisin C is represented by <i>ent</i>-<b>3</b>