Crystal Structure of an Inhibitor of Starfish Embryonic Development, 4-Oxo-7-(β-D-ribofuranosyl)-3H-furo[3,2-d]pyrimidine: Revision of Pyrrolosine Structure

Abstract

We isolated a C-nucleoside from a culture broth conditioned by the actinomycete Streptmyces albus A282 and reported its structure as la.l The substance, being designated pyrrolosine, inhibited the RNA synthesis of starfish (Asterina pectinifera) embryos at blastulation. Recently, we found that the culture broth extract treated with an adenosine deaminase did not prevent the embryonic development at the blastulation stage, which raised a question as to the proposed structure of pyrrolosine in which no amino group exists.The adenosine deaminase treatment of pyrrolosine yielded an unknown product 2, which showed [a]2D -18.8° (c=0.2, H20) and mp 115° C. The molecular formula was determined by SIMS (m/z 269.0774 for MH+, D0.1 mM U). The compound 2 prevented the development of fertilized starfish eggs specifically at the rotating blastula stage at concentrations above 0.8 µg/ ml.A colorless crystal (0.35X0.05X0.01 mm) was obtained from an ethanol solution and used for X-ray analysis. The intensity data were collected with graphite monochromated Cu Ka radiation from a fine-focus rotating anode at 40 kV 80 mA using w/ 1.78 scan in a 26

Selective inhibition of gastrulation in the starfish embryo by albuside B, an inosine analogue

“…It was notable that the nucleus was present in each blastomere of the development-arrested embryo [6]. Similar results were obtained with albuside [4]. These results strongly suggest that the majority of mRNAs necessary for blastula formation are stored in the egg and that transcripts newly synthesized before and during blastulation are required for development to proceed from the early bastula stage.…”

“…Albuside B was converted from albuside (4-amino-7-(fl-D-ribofuranosyl)-furo [3,2- [4]. Albuside (10 mg) was incubated at 25°C for 2 h in 1.2 ml of 5 mM potassium phosphate buffer (pH 7.4) containing 0.2 mg of 200 units/rag calf intestinal adenosine deaminase (EC 3.5.4.4, Boehringer Mannheim).…”

“…The fraction which showed uv maxima at 219 nm and 259 nm (water, pH 7.0) eluting at the retention time of 0.76 relative to that of albuside was collected. Evaporation of the solvents gave a residue (9.0 mg), which was recrystallized from ethanol to afford pure albuside B as colorless needles (melting point, 115°C) [4].…”

“…The present study was initiated in an effort to detect and characterize a selective inhibitor of gastrulation of the starfish (Asterina pectiniJera) embryo as a first step towards understanding the molecular basis of cellular differentiation accompanying gastrulation in the starfish embryo. We have found that fluorescein-isothiocyanate (FITC)-conjugated soybean agglutinin (SBA) specifically stains the progenitor cells of the mesendo- [4], prevents both mesendoderm difl'erentiation and gastrular morphogenesis indicates that these two developmental events are closely related.…”

Expanding Heteroaromatic and 2-Aminosugar Chemical Space Accessible from the Biopolymer Chitin

“…Our ongoing efforts in this area have focused on using the aforementioned N-platforms to access the chemical intermediates used within the pharmaceutical and/or agrochemical sectors. One target that fulfils these criteria is furo [3,2-d]pyrimidin-4-amine 1, a heteroaromatic scaffold found in the C-nucleoside antibiotic pyrrolosine [26][27][28] and employed in a multitude of medicinal chemistry programmes against a diverse range of targets, including spleen tyrosine kinases [29], G protein-coupled receptor 119 [30], p110δ PI3 kinase [31], and FYVE-type finger-containing phosphoinositide kinases [32]. We envisaged that the heteroaromatic ring system 1 could be accessible from 3A5AF via cyanation at C2 followed by acetamide hydrolysis to provide aminonitrile 2 followed by heteroannulation with formamidine [27,28,33,34] (Scheme 2).…”